Christine
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http://www.mdanderson.org/news-and-publ ... ancer.html
When combined with the standard chemotherapy drug Taxotere® (docetaxel), the oral targeted therapy Zactima® (vandetanib) improves progression-free survival for patients with advanced non-small cell lung cancer.
Researchers from M. D. Anderson presented the findings of the first-of-its-kind, international Phase III trial at the American Society of Clinical Oncology's (ASCO) annual meeting in May.
Significance of research: Vandetanib, an oral tyrosine kinase inhibitor, is the first agent to target two lung cancer receptors - Epidermal growth factor receptor (EGFR) and Vascular endothelial growth factor receptor (VEGFR).
"In lung cancer, EGFR targets the tumor cell, and VEGFR targets the blood vessels,” says the study’s international principal investigator, Roy Herbst, M.D., Ph.D., chief of the section of Thoracic Medical Oncology in M. D. Anderson's Department of Thoracic/Head and Neck Medical Oncology. “With vandetanib, we're really targeting the entire tumor environment at the same time.
"As a dual inhibitor, vandetanib may provide cost savings to patients because they potentially can be treated with one therapy instead of two," he says.
According to the American Cancer Society, lung cancer accounts for the most cancer-related deaths in the United States. In 2009, more than 219,000 will be diagnosed with lung cancer, and more than 159,000 are expected to die because of it.
Research methods: The study enrolled 1,391 patients who:
Had non-small cell lung cancer
Were treated at 198 centers across the country
Were treated between May 2006 and April 2008
Had previously received chemotherapy
Participants received either:
Docetaxel and a placebo (inactive substance)
Docetaxel and vandetanib
Median follow-up was 12.8 months.
The study's goal was to examine progression-free survival.
Primary results: Patients who received docetaxel and vandetanib had a 21% higher rate of reduction in disease progression than those who received docetaxel alone.
Median progression-free survival was:
17.3 weeks for those who received both drugs
14 weeks for those who received only docetaxel
While it trended positive, there was no statistical difference in overall survival between the two groups.
Additional resultsL: Although agents that target VEGFR are associated with increased toxicity and side effects that include pulmonary bleeding, patients who received vandetanib experienced fewer significant side effects than those who received docetaxel alone.
People who took vandetanib and docetaxel had minor side effects. These included diarrhea, skin rash, and neutropenia (low level of a type of white blood cells).
Those who took docetaxel alone had more serious side effects. These included: nausea and anemia
What’s next?: "This study will have immediate clinical implications,” Herbst says. “We need to build on this research and turn our focus toward better identifying molecular markers, with the ultimate goal of personalizing care.
"Our ultimate goal always is to improve survival for our patients; however, the improved time to progression with fewer significant effects is important. Hopefully this study will serve as the foundation for the merger of personalization and discovery with now-proven safety and efficacy."
Herbst plans to update the survival data later this year.
Vandetanib also is being studied as a single agent in lung cancer and thyroid cancer.
This article was adapted by Dawn Dorsey from an M. D. Anderson news release.
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http://news.prnewswire.com/DisplayRelea ... 489&EDATE=
Epidermal Growth Factor Receptor Mutation Test May Be Key To Identifying Patient Response to Drug Therapies
ALISO VIEJO, Calif., June 16 /PRNewswire-FirstCall/ -- Clarient, Inc. (Nasdaq: CLRT), a premier anatomic pathology and molecular testing services resource for pathologists, oncologists, and the pharmaceutical industry, today announced the launch of a new gene mutation test that can help physicians select the proper therapy for patients with non-small cell lung cancer (NSCLC). The test, called epidermal growth factor receptor (EGFR) mutation, has been validated as a laboratory-developed test and is now available to physicians and their patients.
"Our new EGFR mutation test can be used as a predictive molecular biomarker to explain why a subset of patients with non-small cell lung cancer may respond to EGFR tyrosine kinase inhibitor (TKI) therapies," said Clarient Chief Executive Officer Ron Andrews. Data from new and ongoing studies confirming the importance of EGFR mutation testing was presented at last week's annual American Society of Clinical Oncology (ASCO) meeting. "This information can help pathologists and oncologists improve the overall management of this difficult disease."
Lung cancer, the most common cause of cancer-related death in men and the second most common cause of cancer-related death in women (after breast cancer), is responsible for 1.3 million deaths annually worldwide. According to the National Cancer Institute, there were more than 215,000 patients diagnosed with lung cancer in 2008. With treatment, the five-year survival rate is approximately 14 percent. NSCLC accounts for approximately 85 percent of all lung cancer cases.
"Most of the data and expert commentary at this year's ASCO meeting concluded that lung cancer was not just one single disease but a number of diseases that could be separated by tumor biology," said Ken Bloom, M.D., Clarient's Chief Medical Officer. "One of the biggest and most exciting findings focused around the use of EGFR mutation to identify patients who are much more sensitive to anti-EGFR tyrosine kinase inhibitors. Recent changes to practice guidelines suggest that EGFR mutation testing is moving towards becoming the standard of care for patients with NSCLC. Since lung cancer is such a deadly disease, these advances in biomarker profiles are considered among the most important ones we've seen in predictive medicine."
EGFR activates an important pathway that leads to cell proliferation, lack of differentiation, enhanced cell survival and gene transcription. A large body of experimental and clinical work supports the view that EGFR is an important target for cancer therapy. There are a number of drugs used for the treatment of NSCLC. Several recent publications reported that virtually all responders to these drugs have well documented mutations in the EGFR gene. Mutations on EGFR can be seen in about 10-15 percent of patients.
"Our ability to rapidly develop and commercialize such a test underscores Clarient's agility as a company and the strategic importance of our partnerships with pharmaceutical companies," Andrews added. "We are now well-positioned to help community pathologists incorporate EGFR mutation testing into the existing work-up for NSCLC, allowing patients to avoid unnecessary toxicities, treatment delays and higher overall cost of therapy. In addition to EGFR mutations, other molecular markers have also been cited to predict patient populations that benefit from other therapies used in patients with NSCLC. We feel that EGFR mutation testing is a significant part of the equation, but we are constantly looking for other pathway markers to provide an even more comprehensive story."
About Clarient
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http://www.forbes.com/feeds/hscout/2009 ... 27982.html
MONDAY, June 15 (HealthDay News) -- Scientists may someday be able to fight lung cancer using gene therapy delivered by an inhalable spray.
In a new study, mice with lung cancer that were treated with a vaporized viral vector twice a week for four weeks had fewer, smaller tumors than untreated mice.
Researchers also found that treated mice had increased apoptosis, or programmed cell death, necessary for healthy tissues, as well as suppressed production of several proteins that contribute to cancer cell growth.
The study, by researchers at Seoul National University in Korea, appears in the June 15 issue of the American Journal of Respiratory and Critical Care Medicine.
"Aerosol delivery targets the lungs specifically and represents a noninvasive alternative for targeting genes to the lung," wrote study author Myung-Haing Cho, a professor at Seoul National University. "The delivery of genes via aerosol holds promise for the treatment of a broad spectrum of pulmonary disorders and offers numerous advantages over more invasive modes of delivery."
In the study, researchers used a lentiviral vector derived from a retrovirus able to infect non-dividing cells, causing lasting genetic changes. The lentiviral vector included a carboxyl-terminal modulator protein (CTMP), which inhibits Akt signaling.
Previous research has shown 90 percent of non-small cell lung carcinomas involve the Akt signaling pathway, according to the study.
Researchers divided mice into three groups: one received the aerosolized CTMP vector, one received the vector alone and one third were untreated.
The mice treated by the CTMP vector had significantly fewer, smaller tumors.
Globally, lung cancer is the most common cause of cancer deaths. Most treatments, including surgery, radiation and chemotherapy, slow progression of the disease only temporarily.
While much research is underway on the use of gene therapy to treat lung cancer, one stumbling block has been finding delivery mechanisms that work.
"Our results demonstrated that lentivirus-mediated CTMP overexpression suppressed Akt activity and inhibited tumor progression," Cho wrote.
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http://www.tampabay.com/news/health/article1009936.ece#
Anthony Allis is a walking public service announcement against smoking and for the options available when lung cancer is discovered early. Walking is the operative word here. He's walking a mile each day and playing golf at least twice a week — even though he'll turn 86 on July 28 and was diagnosed with lung cancer just nine months ago.
He attributes his recovery to a minimally invasive cancer treatment called radio frequency ablation, known as RFA, which is used for early stage and inoperable tumors in the lungs, liver, kidney and bone.
"The difference in him after the procedure was like night to day," said his wife, Adele Allis, a retired pharmacist.
He had been a longtime smoker.
"I'm of Italian descent and figure I'd be in great health if I hadn't smoked," Allis said. "I quit smoking 20 years ago, but smoked for 50. If I was still smoking, I wouldn't be here. "
He may be right. There were 215,020 new lung cancer cases and 161,840 deaths in the United States in 2008, with smoking cigarettes attributed as the predominant cause, according to the National Cancer Institute.
Allis went home from the hospital the day after the procedure, started walking a few days later and was back up to a mile within a week.
He uses a cart when he plays golf but says he walks plenty on the course. He also carries a portable chair for his walks and golf, so he can sit and rest any time he wants.
"I'm doing well now," he said. "This time of the year, I play golf two, maybe three times a week. I'd tell anyone thinking about having RFA to absolutely have it done."
Radio frequency ablation has been around almost 20 years. The nonsurgical, localized procedure transmits radio frequency energy through a tiny needle that creates heat and shrinks or obliterates tumors.
The procedure can replace surgery or can be used in conjunction with surgery, radiation and chemotherapy. When used for inoperable tumors, the procedure can increase a person's survival time and quality of life.
But it's not for everyone. Tumor size matters, and the cancer cannot be close to major blood vessels.
"I was always optimistic," Allis said. "My wife, she's the worrier. Everybody has to die sometime. I've lived a good life, traveled abroad extensively. I love Paris. And over the past 10 years we've visited Italy eight times. We both love Italy, the museums, the art. I've been lucky."
The retired New York City school teacher and Marine who served in Iwo Jima is only 5-foot-41/2-inches tall and 115 pounds.
He likes to stay fit and has lived an active outdoor life, especially since he and Adele moved to Clearwater 15 years ago.
He is an avid reader and a lover of classical music, so much so that he listens to opera on his iPod during his walks.
He especially likes Italian composers Giuseppe Verdi, Giacomo Puccini and Antonio Vivaldi.
He also likes to joke, saying, "I told my wonderful Indian doctors, your Hindu gods have been good to me. They laughed."
Dr. Ash Verma, an interventional radiologist at Mease Countryside Hospital, performed Allis' procedure.
"Cancer in the early stages is usually silent," Verma said. "Since his cancer was caught and treated in the early stages, he did not have many physical symptoms related to it. Left untreated, he would likely have symptoms such as increasing fatigue and shortness of breath from an enlarging mass."
A few years earlier, Allis had survived surgery on the carotid artery in his neck and the insertion of stents in his leg arteries to improve his circulation.
Allis remains cancer free and credits his doctors. Verma gives kudos to Allis.
"I truly believe that a positive attitude goes a long way in a patient's recovery," Verma said. "It allows one to mentally face the many challenges that go along with treatment of cancer, including pain, fatigue, loss of appetite and a myriad of other symptoms.
"Cancer patients often suffer from depression which is not always diagnosed. This hinders their physical recovery and energy level.
"Having a positive attitude allows the patient to look forward to the future and be proactive in their physical and mental recovery. Mr. Allis' energy level is still intact and he is as jovial as ever."
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http://www.forbes.com/feeds/hscout/2009 ... 28025.html
Legislation to let FDA regulate tobacco manufacturing and marketing called long overdue
THURSDAY, June 11 (HealthDay News) -- The U.S. Senate's historic vote late Thursday to give the U.S. Food and Drug Administration control over tobacco products brought cheers from health organizations across the country.
The legislation "will finally put an end to Big Tobacco's despicable marketing practices that are designed to addict children to its deadly products," said John R. Seffrin, CEO of the American Cancer Society Cancer Action Network.
"Senate passage of the 'Family Smoking Prevention and Tobacco Control Act' has the potential to reduce the scourge of tobacco products, which kill more than 400,000 Americans every year," he added.
The bill, already passed by the House and now headed to a bipartisan committee for reconciliation before it gets President Obama's signature, authorizes the FDA to set levels for nicotine and other cigarette ingredients, and requires tobacco makers to list the contents of their products. It also requires the FDA to approve any new products in much the same way that it now does with drugs and medical devices. And it gives the FDA the authority to require stronger warnings on cigarette packaging.
Speaking for the American Heart Association, CEO Nancy Brown said, "The U.S. Senate has taken a bold and courageous step to ensure a healthier future for our children.…The legislation will allow us to protect them from a dirty business that has infiltrated school grounds and homes for many generations," she added. "Too many graveyards are marked by the consequences of the industry's actions. With each puff of a cigarette, smokers increase their risk for heart disease, stroke and other cardiovascular diseases, and Big Tobacco's irresponsible marketing campaigns have made it increasingly difficult to break the cycle of addiction and save lives."
Dr. Douglas W. Blayney, president of the American Society of Clinical Oncology, stated, "Tobacco use is associated with increased risk for at least 15 types of cancer and is responsible for 30 percent of cancer deaths. Lung cancer has emerged from relative obscurity at the start of the 20th Century to become the most common type of cancer today, with 87 percent of all cases attributable to smoking. To reverse this trend, the FDA must be able to step in and regulate these deadly products."
And Dr. Nancy Nielsen, president of the American Medical Association, said, "Passage of this historic legislation by both the House and Senate is a victory for public health over Big Tobacco." She noted, "The actions resulting from this landmark legislation may make people think twice before picking up a cigarette. The sad truth is that tobacco-related deaths are the number one preventable cause of death in the U.S."
And the American Lung Association added this:
"Today marks an historic culmination of a more than 20-year journey to provide the (FDA) urgently needed regulatory control over the tobacco industry," said Paul G. Billings, the American Lung Association's vice president for policy and advocacy. "This long-overdue legislation will protect kids and reduce the terrible human and financial burden caused by tobacco use in this country."
"While we celebrate this notable victory, we recognized that we have yet to win the war," added Charles D. Connor, the lung association president and CEO. "As the FDA tobacco legislation continues its way to the President's desk for signature, we will also continue our work for higher tobacco taxes, smoke-free laws and funding of tobacco control and prevention programs at the state level to reduce tobacco use and save lives."
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http://www.redorbit.com/news/health/170 ... cer_risk/#
Scientists have now revealed how nanoparticles can cause lung damage. In the same research, they reported successfully being able to block the cancer-causing mechanism.
Nanotechnology is a growing sector of research that involves the control of atoms and molecules to create new materials, including many that could have medical applications. Nanotechnology, as an industry, is expected to gain an annual market of about $1 trillion by 2015, researchers said in the June 11 issue of the Journal of Molecular Cell Biology.
Nanoparticles have unusual physical, chemical, and biological properties which scientists hope will be able to improve the effectiveness of drugs and gene therapy.
However, there are concerns that the science has underlying toxicity, including lung damage. Although nanotechnology had been traced to lung damage, scientists had been unsure as to how it causes it.
Chinese researchers discovered that ployamidoamine dendrimers (PAMAMs) – a class of nanoparticles being used in medicine – can result in lung damage by turning on the process of autophagic cell death.
Researchers found that by using an autophagy inhibitor, the cell death was counteracted in mice.
"This provides us with a promising lead for developing strategies to prevent lung damage caused by nanoparticles,” said the study's leader, Dr. Chengyu Jiang, a molecular biologist at the Chinese Academy of Medical Sciences in Beijing, China.
“Nanomedicine holds extraordinary promise, particularly for diseases such as cancer and viral infections, but safety concerns have recently attracted great attention and with the technology evolving rapidly, we need to start finding ways now to protect workers and consumers from any toxic effects that might come with it."
"The idea is that, to increase the safety of nanomedicine, compounds could be developed that could either be incorporated into the nano product to protect against lung damage, or patients could be given pills to counteract the effects.”
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http://www.naturalnews.com/026435_asbes ... ancer.html
(NaturalNews) For more than a year Health Canada held on to a report that concluded there is a "strong relationship" between lung cancer and chrysotile asbestos mined in Canada. The report was authored by a panel of international experts and was received by Health Canada in March 2008.
Trevor Ogden, the panel chairman for the report, made repeated requests to Health Canada to have the report made public, but the requests were resisted. Ogden referred to the delay as "an annoying piece of needless government secrecy."
The report was obtained by Canadian media outlet Canwest News Service under Access to Information legislation, but only after 10 months of processing.
The panel's report found a less certain connection between chrysotile asbestos and mesothelioma, a rare form of cancer. However, the report did find a strong connection between chrysotile asbestos and lung cancer, according to Ogden writing in an introductory letter.
In the letter, Ogden, who is editor-in-chief of The Annals of Occupational Hygiene in Britain, also noted that the panel included members who have previously expressed opposing views on the subject, including industry consultant David Bernstein, who was previously involved with asbestos producer Union Carbide Corp, as well as Canadian and California asbestos mining companies.
A Health Canada spokesman said the delay in releasing the report was due to taking time necessary to carefully review the report's findings and to consult other federal and provincial partners.
Leslie Stayner, director of epidemiology and biostatistics at the University of Illinois School of Public Health, commented on details of the report which also included amphibole asbestos as having a connection to risk of mesothelioma.
"The most important thing is what it doesn't say, which is some people have alleged it would say. What it doesn't say is that exposure to chrysotile asbestos is safe," said Stayner. "I think the bottom line here is that all forms of asbestos cause both mesothelioma and lung cancer. We will probably for many years still be debating this question of relative hazard of chrysotile. The fundamental question of whether it's hazardous or not is clear. I think the answer to that is, yes, chrysotile is a hazardous substance."
The report's release has reopened debate on the future of the asbestos industry in Canada, and particularly in the province of Quebec where the industry is concentrated.
Member of Parliament Pat Martin, who has long been a supporter of a ban on Canada's asbestos industry, said the panel's conclusions should be taken seriously and should initiate government action on the matter.
"It makes our case. The reality is we're at a tipping point. The jig is up for the asbestos industry," said Martin, who once worked in an asbestos plant in Yukon without being warned of the health risks. Most uses of asbestos are banned in Canada, and all uses for all forms of asbestos have been banned in Europe and Australia. But Canada remains one of the world's chrysotile asbestos exporters in the world with more than $100 million of exports in 2008, primarily to developing countries like India and Indonesia.
Other countries that have imported Canadian asbestos since 2007 include the U.S., Columbia, Brazil, Peru, Pakistan, China, and Ecuador. Countries that have banned all types of asbestos without exceptions include Bulgaria, Egypt, Poland, Saudi Arabia, Uraguay, Chile, and Iceland.
Chrysotile asbestos is the most commonly encountered form of asbestos, accounting for about 95% of asbestos found in the United States.
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http://www.wowt.com/news/headlines/47886667.html
John Atkinson, who gained national publicity in a celebrity US Open golf contest, passed away at his Omaha home on Thursday June 11, 2009 after a lengthy battle with lung cancer.
Atkinson was diagnosed with lung cancer in 2007 at the age 38. He was a non-smoker.
He became an advocate for lung cancer awareness and was able to advance that message nationwide through the round of golf televised in June 2008 on NBC.
The event was sponsored by Golf Digest Atkinson was selected to play when his essay was judged the winner in a contest that attracted more than 56-thousand entries.
Participants were challenged to break 100 on the US Open layout at Torrey Pines in San Diego and although Atkinson failed in his attempt, he received tremendous support in his efforts to help others affected by lung cancer.
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http://smartabouthealth.net/diseases/20 ... ng-cancer/
Boston (SmartAboutHealth) - It is being reported that scientists have managed to develop a method of reducing one way that people can get lung cancer.
They were able to do this by figuring out a way of blocking nanoparticles from entering into a person’s lungs, thus reducing their overall risk of developing the deadly form of cancer.
The little particles, microscopic in size have been shown to have cancer causing effects, thus by being able to block them from entering the lungs, the risk of lung cancer developing is greatly reduced.
Writing in the Journal of Molecular Cell Biology. Journal of Molecular Cell Biology the scientists explain how they were able to figure out their discovery.
Working with mice, the scientists explain how they injected them with a type of autophagy inhibitor and then exposed them to the toxic particles which had no effect on the lungs of the test rodents.
“This provides us with a promising lead for developing strategies to prevent lung damage caused by nanoparticles,” said the leader of the team, Chengyu Jiang, a molecular biologist at the Chinese Academy of Medical Sciences in Beijing.
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http://www.curetoday.com/index.cfm/fuse ... le_id/1122
BY ELIZABETH WHITTINGTON
A large phase III study, which examined whether the addition of Tarceva (erlotinib) to Avastin (bevacizumab) delayed progression of advanced non-small cell lung cancer, reached its primary goal.
The ATLAS trial included 743 patients treated with four cycles of Avastin and randomized them to continue on Avastin with or without the addition of Tarceva. Data revealed that cancer growth was delayed for 4.8 months with the combination regimen compared with 3.7 months for Avastin alone—a 39 percent improvement. As demonstrated in previous trials, patients who were never-smokers and of Asian descent appeared to have a better response.
The trial was halted after a clear benefit was shown, and patients assigned to the Avastin-only arm were allowed to cross over to receive Tarceva. Overall survival results are expected later this year. Side effects occurred in 44 percent of patients taking Tarceva and Avastin compared with 30 percent receiving Avastin alone, with rash, diarrhea, and fatigue occurring more frequently with the combination.
The next step, researchers say, is to determine if there are biomarkers, such as epidermal growth factor receptor and KRAS mutation, which may have contributed to the success or failure of the treatment in certain patients.
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http://www.curetoday.com/index.cfm/fuse ... le_id/1117
BY ELIZABETH WHITTINGTON
An international phase III trial found the investigational lung cancer drug, Zactima (vandetanib), significantly slowed the time a patient’s advanced lung cancer progressed. The trial, which included nearly 1,400 patients who progressed on prior therapy, compared Taxotere (docetaxel) in combination with either placebo or Zactima.
While the data do not show an overall survival advantage, patients on the Zactima arm had a median progression-free survival of 17.3 weeks compared with 14 weeks with Taxotere alone. Zactima works by blocking both vascular endothelial growth factor, which is instrumental in blood vessel growth to the tumor, and the epidermal growth factor receptor, a protein that spurs malignant cell growth.
Common side effects with Zactima are diarrhea, rash, and neutropenia, which can increase the risk of infection. With the progression-free survival benefit demonstrated, AstraZeneca, the drug’s manufacturer, is planning to submit the drug for Food and Drug Administration approval in the coming months. The drug is also being tested in thyroid cancer.
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http://www.curetoday.com/index.cfm/fuse ... inhibitors
By: Melissa Weber
If you're receiving an EGFR inhibitor to treat your cancer, I have some good news. Doctors now know how to prevent the skin rash that develops in up to 90 percent of patients receiving these drugs.
A combination of sunscreen, moisturizers, topical corticosteroids, and the oral antibiotic doxycycline reduced the incidence of severe rash by more than half when given to patients before Vectibix, compared with patients who were treated after the rash developed. The study was reported today at ASCO's annual meeting, and presenter Edith Mitchell, MD, of Thomas Jefferson University in Philadelphia, told reporters that her institution has already implemented the rash prevention strategy.
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As if having to undergo a kidney transplant wasn't traumatic enough, singer Natalie Cole endured the tragedy of having her sister die while she was undergoing the operation, the New York Post reports. Cole was with her sister, Carole "Cookie" Cole, when she got the call that an organ was available. Natalie's other sister, Timolin Cole, told the Post that Natalie was reluctant to leave her dying sister, who had only been diagnosed with lung cancer the week before. "I told her, 'Natalie, this is God's gift, and you've got to go now. Cookie would want this for you.' " Natalie, who has hepatitis C and required dialysis three times a week, had a successful surgery, and is expected to go home over the weekend. Cole's father, Nat King Cole, also died of lung cancer, in 1965.
[Photo]
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http://www.cancerwise.org/march_2009/di ... olor=green
When Glynn Kron went to his doctor in October 2007 to ask for help to quit smoking, he knew he was doing the right thing. But he had no idea that visit would save his life.
The doctor wanted to look at an X-ray of Kron’s lungs before he would prescribe Chantrix® (varenicline), a medication that helps suppress the urge to smoke. To Kron’s surprise, the X-ray revealed a collapsed lung that wouldn’t re-inflate. The lining of his lung was covered in malignant tumors. A biopsy confirmed that Kron, 56 at the time, had mesothelioma.
Mesothelioma is a cancer of the lining of internal organs, while malignant pleural mesothelioma is a cancer of the lining of the lungs, usually caused by long-term exposure to asbestos. People who worked in construction or manufacturing, especially before asbestos was removed from most products in the 1980s, or those who have renovated older houses, are most likely to have been exposed. Usually, people are unaware they have been exposed to asbestos.
Kron is one of those people. He has no clue when he might have been around asbestos. Earlier in life he did some construction work, nothing in demolition, and worked on cars, but he can’t recall being exposed to asbestos.
Although Kron was surprised, he didn’t panic about the diagnosis.
“I accepted the fact that I had a problem, and I just knew I wanted to fix it,” he says.
An oncologist close to Kron’s Louisiana home proposed treating the mesothelioma with chemotherapy and predicted Kron had only a few years to live. But Kron says he didn’t want to accept this treatment as the only option; he wanted a chance to rid himself of cancer entirely.
“I told the doctor his prediction was unacceptable,” Kron says. “I wanted to go to a cancer treatment center, so he referred me to M. D. Anderson.”
Besides finding other methods of treatment at M. D. Anderson, Kron discovered a different attitude toward the future.
“The doctors at M. D. Anderson didn’t tell me how long I had to live,” Kron says. “They don’t know, and neither do I. That’s how I look at it. We just don’t know.”
Some people expected him to be depressed by the diagnosis, as if cancer is a life sentence. But he says he found a source of optimism and strength in his faith in God.
“I delved a little deeper into religion,” he says. “I prayed a lot to get my cancer cleared up, and my prayers were answered.”
In addition to his faith, Kron’s sister was a source of support for him. She accompanied him on the long trips from Louisiana to Houston, a gesture he appreciates.
“She helped quite a bit just by being there to support me,” he says.
Despite the serious diagnosis, Kron was confident of his decision. In January 2008, surgeons at M. D. Anderson removed the tumors and Kron’s left lung. The surgery was followed by five weeks of targeted radiation treatment.
Today, he has been cancer-free for one year.
While recovering from the extensive treatment was painful, Kron couldn’t give up other obligations. He’s the caregiver for his 85-year-old father.
Kron has returned to his job at a petroleum-testing lab and plans to stay on for at least a few more years. Life hasn’t gotten back to “normal” yet, but he did meet the goal he made going into the doctor’s office that fateful day: He quit smoking.
Although he tires easily and has pain at the surgery site, Kron says he’s learned to live with the situation and gets by just fine.
“You learn to live with things the way they are,” he says. “You accept it and go about your business. You have to find the best care you can, and you have to have faith that everything is going to turn out OK. And you have to give it time.”
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http://www.cancerwise.org/February_2009 ... isplayFull
We are told stress relief is a few deep lungfuls of air away, but for many cancer patients deep, relaxing breaths aren’t easy to come by.
M. D. Anderson’s Department of Rehabilitation Services offers training in breathing techniques, in conjunction with physical therapy, to help patients use their lung capacity to breathe easier and in a more relaxed manner.
Physical Therapy Supervisor Janet Scheetz says breathing practices can be helpful to anyone.
They are especially beneficial for patients with:
* Lung cancer
* Chronic obstructive pulmonary disease (COPD)
* Emphysema
* Asthma
* Fibrosis (scarring) or fluid buildup in the lungs caused by radiation treatment
Work on perfecting posture
One of the most common problems is incorrect breathing posture. Patients with ineffective breathing patterns often adopt poor posture, further reducing their lung capacity.
“When you have difficulty breathing, it is often reflected in your posture,” Scheetz says. “We encourage patients to practice proper posture while sitting, standing and walking: Keep the back straight and the shoulders relaxed.”
Scheetz says she teaches patients several methods to help expel air from the lungs and bring enough air back in. These methods can be used when a person feels breathless or just wants to relax.
Some of the most common techniques are:
Diaphragmatic breathing:
* Breathe in deeply through the nose
* Instead of moving shoulders up or down, push the belly out
* Pause for one second
* Breathe out through the nose, sucking the belly back in
The upper chest should remain still because the breathing is taking place through the diaphragm. Don’t breathe too deeply for too long because it can cause dizziness.
Pursed-lip breathing:
* Sit in a chair with a straight back
* Relax the neck and shoulder muscles
* Breathe in slowly through the nose for two seconds with the mouth closed
* Pucker lips as if to whistle
* Slowly breathe out while counting to four
* Do not forcefully exhale
Controlled coughing:
* Sit in a chair with a straight back and place feet flat on the floor
* Cross the arms in front or wrap a sheet around stomach and hold the ends
* Take slow, deep breaths through the nose and hold for two counts
* Lean forward slightly
* Use arms to softly push on stomach while breathing out
* Perform two short coughs, but no more
* Rest and repeat
This method can be used when a person has repeated coughing fits that may create breathlessness and not fully clear the lungs.
Proper breathing improves quality of life
Patients are asked to determine “perceived breathlessness” while they perform physical tasks, such as walking, performing daily activities or exercising.
Perceived breathlessness is the severity of breathlessness during physical activity. This measurement helps determine when patients should use the breathing practices at home.
The breathing therapy process is geared toward patients’ level of comfort. They are encouraged to share their levels of perceived breathlessness to prevent overexertion.
“We’re trying to help patients find out what they can do safely, efficiently and effectively so that they achieve the most benefit from what they are doing,” Scheetz says.
Proper breathing enables patients to have a better quality of life and lets them do more of the things they enjoy, Scheetz says. But she adds people need to know their limits and not overexert themselves during everyday physical activity.
Scheetz says step-by-step increases in physical activity and the use of breathing techniques help patients feel comfortable while being active at home.
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http://www.cancerwise.org/February_2009 ... isplayFull
Patients with locally advanced non-small cell lung cancer who are treated with proton beam therapy and chemotherapy may have fewer instances of bone marrow toxicity than patients who receive the standard treatment of intensity-modulated radiation (IMRT) and chemotherapy.
This may help them avoid some side effects and withstand more aggressive treatment.
This first-of-its-kind study was reported by M. D. Anderson researchers at the November 2008 Chicago Multidisciplinary Symposium in Thoracic Oncology.
Significance of results
Lung cancer is the leading cause of cancer death in the United States, according to the American Cancer Society. In 2008, approximately 215,000 people will be diagnosed with lung cancer, and approximately 114,000 people will die from the disease.
IMRT and chemotherapy, the standard of care for this type of cancer, provide a 25% five-year survival rate, the best outcomes available. But this method of treatment also carries a high risk of bone marrow toxicity and unpleasant side effects.
Bone marrow toxicity lessens the amount of hemoglobin, neutrophils, lymphocytes and white blood cells in patients’ blood. This further weakens their already compromised immune systems and can make it even more difficult to withstand aggressive treatment. Bone marrow toxicity can lead to infection, bleeding, fatigue and even death.
"As a physician, I have seen how IMRT and chemotherapy affect patients' overall health. They are tired, suffer from night sweats, are prone to infection and have to compromise their treatment,” says Ritsuko Komaki, M.D., professor in M. D. Anderson's Radiation Treatment Center and lead author on the study.
"Our goal is to find the best way to treat the cancer without further weakening the patient,” she says. “With proton therapy, we may now have an option that lessens this toxicity so that treatment dosage can be maximized."
Protons are heavier than X-rays, allowing them to travel in straight paths through the body without being deflected. Proton beam therapy strips away the electrons in cancer cells, mutating the cells' structure so they cannot divide and multiply. While standard radiation therapy destroys the tumor and the healthy tissue around it, proton therapy can target a tumor precisely with little damage to normal tissue.
Proton beam therapy may be especially valuable for patients who are the most vulnerable to bone marrow toxicity or those whose normal cells are growing, such as children.
"Proton therapy may promise safer and more effective treatment for children, whose bone marrow is still developing, and elderly patients who are more prone to complications and cannot withstand aggressive treatment,” says James Cox, M.D., professor and head of M. D. Anderson’s Division of Radiation Oncology and the study's senior author.
Background
This is the first study to examine the benefits of proton beam therapy and concurrent chemotherapy in advanced lung cancer patients.
Research methods
Researchers compared bone marrow toxicity levels in 142 patients treated for lung cancer between January 2003 and June 2008. All of the patients received chemotherapy.
In addition:
* 75 patients were treated with IMRT
* 67 patients were treated with proton beam therapy
Primary results
After 17 months, patients treated with chemotherapy and proton beam therapy experienced significantly less reduction in hemoglobin, neutrophils and lymphocytes.
What’s next?
M. D. Anderson is working with Massachusetts General Hospital to enroll patients in a clinical trial to confirm these initial findings.
-Adapted by Dawn Dorsey from an M. D. Anderson news release. http://www.mdanderson.org/departments/n ... 508b603a14
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http://www.cancerwise.org/february_2009 ... &color=red
A novel combination of carboplatin, Taxol® (paclitaxel), and the targeted therapies Avastin® (bevacizumab) and Erbitux® (cetuximab) is safe and may extend the lives of patients with advanced lung cancer, according to a recent study.
Edward Kim, M.D.Lead author and study principal investigator Edward Kim, M.D., assistant professor in the Department of Thoracic/Head and Neck Medical Oncology, conducted the Southwest Oncology Group (SWOG) Phase II study, the first to pair the standard regimen of carboplatin, Taxol and Erbitux with Avastin. Results were presented in November at the 2008 Chicago Multidisciplinary Symposium in Thoracic Oncology.
Significance of results
Lung cancer is the leading cause of cancer death in the United States, according to the American Cancer Society. In 2008 approximately 215,000 people were diagnosed with lung cancer, and approximately 114,000 died from the disease.
The study looked to increase effectiveness of the standard regimen for lung cancer without compromising patient safety.
“Due to toxicity concerns of standard cytotoxic chemotherapy, we could not conduct a study with four chemotherapeutic agents,” says Kim, principal investigator. “But after another study showed that Avastin enhances the efficacy of existing therapy, we wanted to see whether it might improve the carboplatin-paclitaxel-Erbitux combination.”
Data in lung cancer also have suggested an enhanced effect in pairing the epidermal growth factor (EGFR) inhibitor compounds with the vascular endothelial growth factor (VEGF) inhibitor, Kim adds.
Research methods
Between August 2006 and September 2007, the Phase II study enrolled 110 stage IIIB or IV non-small cell lung cancer patients. Ninety-nine were eligible for evaluation. Patients received six cycles of the four-drug regimen and continued receiving Avastin and Erbitux as maintenance therapy.
It's unique for a trial to feature a maintenance therapy combining two biologic drugs, Kim explains.
Primary results
The study met its primary endpoint, safety, which was defined by frequency of pulmonary hemorrhage (bleeding), a concern related to Avastin. There were four deaths related to treatment and two due to bleeding, which is consistent with prior Avastin studies.
Adverse events such as low blood counts and neuropathy were reported in 40 patients, which is consistent with standard chemotherapy.
Secondary endpoints included response rate, progression-free survival and overall survival.
Of patients enrolled:
* 53% experienced shrinkage of their tumors
* 24% had stable disease
The median progression-free survival rate was seven months, and overall survival was 14 months. In contrast, previous studies showed an average progression-free survival rate of 5½ months and overall survival of 12 months.
What’s next?
"These compelling findings are the best results ever for a SWOG-based study in advanced lung cancer,” Kim says. “While results are in early stages, this four-drug combination seems to show modest, yet promising, improvement without compromising patients' safety.
"Next, we’ll analyze the tissue from this study to find appropriate biomarkers for the disease to best understand who might benefit from this drug regimen."
A biomarker analysis of this study is ongoing, and a randomized Phase III study is planned to open in 2009.
-Adapted by Mary Brolley from an M. D. Anderson news release.
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01/09/2009
Associated Press
David Arthur Roberts, a left-handed pitcher who played for eight Major League teams including the 1979 World Series champion Pittsburgh Pirates, has died of lung cancer. He was 64.
Roberts' wife Carol and stepdaughter Kristy Rogan say he died at his home in Short Gap early Friday morning.
They say he developed lung cancer from asbestos exposure as a young man. During the off seasons, he worked as a boilermaker and was regularly exposed to the cancer-causing material.
Roberts had a 12-year career in Major League Baseball, beginning in 1969 with the San Diego Padres and ending in 1981 with the New York Mets.
In between, he played with the Pirates, Houston Astros, Detroit Tigers, Chicago Cubs, San Francisco Giants and the Seattle Mariners.
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http://www.tri-cityherald.com/kennewick ... 07625.html
State Rep. Bill Grant, D-Walla Walla, has been diagnosed with a rare form of lung cancer, he announced Friday.
Grant was unavailable for comment Friday and did not indicate in a statement if the diagnosis changes his plans for the upcoming Legislative session or the rest of his term.
The 71-year-old Walla Walla native was re-elected last month to serve the 16th Legislative District, which covers portions of Benton and Franklin counties -- including east Kennewick and all of Pasco -- and all of Walla Walla and Columbia counties.
Grant has served for 22 years.
The fourth-generation wheat farmer was diagnosed with cancer in Seattle after his doctor recommended he travel there for a lung biopsy, his statement said.
Grant did not specify what kind of lung cancer he has, but said the Seattle oncologist sees only a few cases a year of the rare cancer.
"Although these are not the results I had hoped for, the good news is I have been released from the hospital and am heading home to discuss my treatment options," he said. "I thank you for all your concerns and would appreciate your positive thoughts and prayers directed my way.
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http://www.cancerwise.org/December_2008 ... isplayFull
Whole-Brain Radiation Affects Learning, Memory
Treatment for Metastasized Cancer Often Impairs Function
When patients with cancer that has metastasized (spread) to the brain are treated with whole-brain radiation therapy (WBRT), their risk of developing learning and memory problems increases dramatically.
A Phase III study at M. D. Anderson showed that pairing WBRT with stereotactic radiosurgery (SRS), a type of targeted radiation therapy, doubles the risk of learning and memory problems compared to treatment with SRS alone.
Results of the study were presented at the annual meeting of the American Society for Therapeutic Radiology and Oncology.
Significance of Results
This year, about 170,000 cancer patients will experience metastases to the brain from common primary cancers such as breast, colorectal, kidney and lung, according to the American Cancer Society.
"Determining how to achieve the best outcomes with the smallest cost to the quality of life is a treatment decision every radiation oncologist faces," says Eric Chang, M.D., associate professor in the Division of Radiation Oncology at M. D. Anderson.
"While WBRT and SRS are in practice and equally acceptable, data from this trial suggest that oncologists should offer SRS alone as the upfront, initial therapy for patients with up to three brain metastases,” he says.
Background
SRS has become widely used over the past decade as an initial treatment for cancers that have spread to the brain. It is often combined with WBRT.
The study builds on previous research by senior author Christina Meyers, Ph.D., chief of the Section of Neuropsychology in the Department of Neuro-Oncology at M. D. Anderson, which examined memory and learning problems in patients with brain metastases treated with WBRT.
Research Methods
This seven-year study observed 58 patients with one to three newly diagnosed brain metastases.
They were assigned randomly to receive either:
SRS followed by WBRT
SRS alone
Using standardized tests, researchers measured participants' learning and memory function before and after treatment.
Primary Results
Approximately four months after treatment, learning and memory function declined in:
49% of patients who received SRS plus WBRT
23% of patients who received SRS alone
An independent data monitoring committee stopped the study after early results showed most patients (96.4%) performed better when treated with SRS alone.
"The risks of learning dysfunction outweigh the benefits of freedom from progression and tip the scales in favor of using SRS alone,” Chang says.
Additional Results
"Unlike past studies comparing the two treatment strategies that did not use sensitive cognitive tests or closely follow patients after being treated with SRS alone, radiation oncologists in this trial were able to identify new lesions early and treat them," Meyers says. "We believe doctors and patients alike will favor this method instead of SRS plus WBRT as an initial treatment."
What’s Next?
Based on these results, future research will study patients with more than three brain metastases being treated with SRS alone and compare them to patients treated with WBRT alone, the current standard of care.
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http://www.reuters.com/article/healthNe ... OI20081113
Four drug combination helps in lung cancer: U.S. study
Thu Nov 13, 2008 12:52pm EST
By Maggie Fox, Health and Science Editor
WASHINGTON (Reuters) - Combining two chemotherapy drugs with two targeted therapies was safe and appeared to help patients with advanced lung cancer live longer, U.S. researchers reported on Thursday.
The combination of Roche and Co's Avastin, ImClone's Erbitux, carboplatin and paclitaxel appeared to add an average of two months to the lives of patients, from 12 months on average to 14 months, the team at the University of Texas M. D. Anderson Cancer Center said.
It was the first time two targeted therapies were used together with traditional chemotherapy in this way and M.D. Anderson's Dr. Edward Kim said the Avastin and Erbitux appeared to work synergistically.
"The rationale behind the study was the finding that Avastin enhances the efficacy of existing therapy, thereby possibly improving the carboplatin-paclitaxel-Erbitux regimen," Kim said in a statement.
"While early, this four-drug combination seems to show promising, yet modest improvement in efficacy without compromising patients' safety," Kim added.
He said his team would analyze the tumors to see if there were so-called biomarkers that can predict who would do best on this therapy.
Avastin, known generically as bevacizumab, is a monoclonal antibody, a genetically engineered immune system molecule, that targets vascular endothelial growth factor or VEGF. VEGF helps tumors grow a blood supply and Avastin is a so-called angiogenesis inhibitor that helps choke off that supply.
Erbitux, known generically as cetuximab, is also a monoclonal antibody and angiogenesis inhibitor but it targets a different blood-vessel-promoting molecule called epidermal growth factor receptor or EGFR.
The two older chemotherapy drugs, paclitaxel, sold under the brand name Taxol and carboplatin sold under the brand name Paraplatin, both by Bristol Myers Squibb, kill tumor cells directly.
Kim told the 2008 Chicago Multidisciplinary Symposium in Thoracic Oncology that his team tested 110 patients with stage 3 or 4 lung cancer in a phase II safety and efficacy trial.
The patients got six cycles of all four drugs and then as maintenance continued infusions of Avastin and Erbitux.
Four patients died from the treatment -- Avastin is known to sometimes cause internal bleeding -- and 40 patients had the usual side effects such as nerve pain and low blood counts.
But 53 percent had their tumors shrink and 24 percent had stable disease. On average patients enjoyed seven months before their tumors started growing again and lived 14 months.
Patients who previously got three drugs without Avastin lived an average of 5.5 months before their tumors started to grow again and 12 months overall.
Lung cancer is the leading cause of cancer death globally, with 1.2 million deaths a year and 114,000 annually in the United States, according to the American Cancer Society.
While many drugs are used to treat lung cancer, they almost all stop working eventually.
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http://in.reuters.com/article/health/id ... 6620080916
ZURICH/LONDON (Reuters) - The results of a study presented on Monday show that Avastin combined with gemcitabine-cisplatin chemotherapy improves the time lung cancer patients live without progression of the disease, according to Swiss drugmaker Roche. There was also a positive trend to extended survival.
Patients with previously untreated, advanced non-small cell lung cancer (NSCLC) survived up to 30 percent longer without disease progression when Avastin was added to the treatment regimen, according to a final analysis of the "Avail" trial presented at the European Society of Medical Oncology in Stockholm.
The tumor response rate increased by up to 70 percent compared with chemotherapy alone, Roche added.
Roche, which is a partner with Genentech in Avastin development, said the study was not powered to demonstrate an overall survival benefit.
As a result -- as previously announced -- there was no statistically significant difference in survival between those who did and did not receive Avastin.
But there were some encouraging signs.
An exploratory analysis of overall survival in patients without second-line therapies showed a trend towards improvement of survival in patients given Avastin compared with those given chemotherapy alone, from 7.3 months to 8.7 months.
All treatment groups in the study demonstrated an average overall survival of more than 13 months.
"Avail confirms for the second time that Avastin provides important clinical benefits and the longest survival reported for patients with advanced non-squamous NSCLC," said Christian Manegold of Heidelberg University in Mannheim, Germany, the principal investigator of the study.
Avastin works by directly inhibiting vascular endothelial growth factor, a key mediator of the growth of new blood vessels. The lack of blood vessels prevents oxygen from reaching the tumor cells and they die.
The drug is approved in different countries as a treatment for colorectal, lung, breast and kidney cancer.
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http://info.cancerresearchuk.org/news/a ... r/18776764
People who have a family history of lung cancer and genetic variations in a particular region of DNA are more than five times more likely to develop lung cancer than other people, US scientists have found.
Researchers at Washington University School of Medicine found that a narrow region on chromosome 15 contains genetic variations that are strongly associated with lung cancer in people with a family history of the disease, regardless of whether or not the individuals are smokers.
This region of DNA has now been implicated in the development of lung cancer in a number of studies, raising hopes that a genetic test could be used to alert people to their high risk.
Senior author Dr Ming You, of the university's Siteman Cancer Centre, noted that many smokers do not get lung cancer, suggesting that genetics are also involved.
"We also know that some families have a high incidence of lung cancer," he continued. "If we can identify the genetic factors linked to lung cancer in such people before they get the disease, we can take steps to help prevent it. This genetic region might be part of the answer."
The researchers compared DNA samples of 194 Caucasian people with a strong family history of lung cancer with those of 219 similar people over the age of 60 with no history of the disease.
Their DNA was screened for more than 300,000 known genetic variations and the researchers identified several which were strongly associated with inherited lung cancer, with the most strongly linked appearing on chromosome 15.
These genetic variants were much more common in people with lung cancer than with people who were cancer-free.
Dr You said that the findings, which appear in the Journal of the National Cancer Institute, may be "very important information".
"It would suggest that specific genes in this region and smoking are independent risk factors for lung cancer, and together they might cause an even greater increase in lung cancer risk."
Dr You added: "These genes play roles in cellular proliferation and cell death. And they are active in lung cancer tumours. More research will be needed to fully delineate the part they play in lung cancer and whether they will be good targets for cancer therapies in the future."
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http://www.economist.com/science/displa ... d=12202589
Cancer may be caused by stem cells gone bad. If that proves to be correct, it should revolutionise treatment
MUCH of medical research is a hard slog for small reward. But, just occasionally, a finding revolutionises the field and cracks open a whole range of diseases. The discovery in the 19th century that many illnesses are caused by bacteria was one such. The unravelling of Mendelian genetics was another. It now seems likely that medical science is on the brink of a finding of equal significance. The underlying biology of that scourge of modern humanity, cancer, looks as though it is about to yield its main secret. If it does, it is possible that the headline-writer’s cliché, “a cure for cancer”, will come true over the years, just as the antibiotics that followed from the discovery of bacteria swept away previously lethal infectious diseases.
The discovery—or, rather, the hypothesis that is now being tested—is that cancers grow from stem cells in the way that healthy organs do. A stem cell is one that, when it divides, produces two unequal daughters. One remains a stem cell while the other multiplies into the sorts of cells required by its organ. This matters for cancer because, at the moment, all the cells of a tumour are seen as more or less equivalent. Therapies designed to kill them do not distinguish between them. Success is defined as eliminating as many of them as possible, so those therapies have been refined to do just that. However, if all that the therapies are doing is killing the descendants of the non-stem-cell daughters, the problem has not been eliminated. Instead of attacking the many, you have to attack the few. That means aiming at the stem cells themselves.
Not all investigators support the cancer-stem-cell hypothesis, but the share who do so is growing rapidly. A mere five years ago, few research papers on the subject were presented at big academic meetings. This year there were hundreds at one such meeting alone. Moreover, data from clinical trials based on the hypothesis suggest that it has real value for patients. As a result, drug companies have taken notice and are trying to develop substances that will kill cancer stem cells.
The virtues of self-restraint
The root cause of both cancer and stem cells is multicellularity. In the distant past, when all living things had only one cell, that cell’s reproduction was at a premium. In the body of an animal, however, most cells have taken a vow of self-denial. Reproduction is delegated to the sex cells. The rest, called somatic cells, are merely supporting actors, specialised for the tasks needed to give the sex cells a chance to get into the next generation. For this to happen required the evolution of genes that were able to curb several billion years’ worth of instinct to proliferate without killing that instinct entirely. Only then could somatic cells do their job, and be present in appropriate numbers.
The standard model of tumour formation was based on the fact that somatic cells slowly accumulate mutations. Sometimes these disable the anti-proliferation genes. If enough of the brakes come off in a somatic cell, so the theory went, it will recover its ancestral vigour and start growing into a tumour. Cancer, then, is an inevitable cost of being multicellular.
The discovery of stem cells changed this picture subtly, but importantly. Blood stem cells were found a long time ago, but only recently has it become apparent that all tissues have stem cells. The instincts of stem cells lie halfway between those of sex cells and ordinary body cells. They never stop reproducing, but they cannot look forward to making the generational leap. When the body dies, so do they. However, they are few in number, and because at cell division only one daughter continues to be a stem cell, that number does not grow.
This division of labour may even be another type of anti-cancer mechanism. It allows stringent locks to be put on somatic cells (which, for example, strictly limit the number of times they can divide), yet it permits tissue to be renewed. Without stem cells, such tissue-renewal would be the province of any and every somatic cell—a recipe, as the traditional model observes, for tumorous disaster. The obverse of this, however, is that if a stem cell does mutate into something bad, it is likely to be very bad indeed. That, in essence, is the stem-cell hypothesis of cancer.
One obvious prediction of this hypothesis is that tumours will have at least two sorts of cell in them: a dominant population of daughter cells and a minority one of stem cells. The first person to show that to be true was John Dick, a molecular biologist at the University of Toronto. In 1997 he isolated what looked like stem cells from a blood cancer called acute myeloid leukaemia (AML). Blood cancers are easier to deal with in this context than solid tumours because their cells do not have to be separated from one another before they are examined. One characteristic of AML cells is that they have two sorts of a protein, called CD34 and CD38, on their surfaces. Dr Dick thus used two sets of special antibodies for his experiment. One sort stuck only to the CD34 molecule, the other only to CD38. Each sort was also attached to a fluorescent tag.
By mixing the AML cells from his patients with the two antibodies and running them through a machine that sorted them according to how they fluoresced, he showed that most were positive for both proteins. However, a small fraction (as low as 0.2%) were positive only for CD34. These, he suspected, were the stem cells.
He was able to confirm this by injecting the minority cells into mice. The resulting tumours had the same mix of cells as those from human patients. However, when he injected mice with samples from the majority cells, with both sorts of the protein, no tumours resulted. The CD34-only cells thus acted as cancer stem cells.
Moreover, this phenomenon was not confined to leukaemia. In 2003 a group of researchers at the University of Michigan in Ann Arbor, led by Max Wicha and Michael Clarke, used a similar trick on breast-cancer cells. In this case the surface proteins were known as CD24 and CD44, and the minority were those positive only for CD44. As with AML, these minority cells produced cancers in mice, whereas the majority cells did not.
Since these two pieces of work, the list of cancer stem cells has multiplied. It now includes tumours of the breast, brain, prostate, colon, pancreas, ovary, lung, bladder, head and neck, as well as melanoma, sarcoma, AML, chronic myelogenous leukaemia, Hodgkin’s lymphoma and myeloma.
That is quite a list. The question is, what can be done with it? Jeremy Rich, a neurologist at Duke University in Durham, North Carolina, has one idea. He created mice that had human glioblastoma tumours, a form of brain cancer, growing in them. Then he treated these mice with radiation (the standard therapy for such cancer in people). He found that the cancer stem cells were more likely to survive this treatment than the other cells in the tumour. That turned out to be because, although all the tumour cells suffered equal amounts of DNA damage from the radiation, the stem cells were better able to repair this damage. When he treated the mice simultaneously with radiation and with a drug that interferes with DNA repair, however, the stem cells no longer had an advantage. They were killed by the radiation along with the other cells.
If that result applies to people as well as rodents, it opens up a whole avenue of possibility. In fact, Dr Rich is now in negotiations with several companies, with a view to testing the idea in humans. That “if” is a real one, though. A mouse is not a human being.
Indeed, the stem-cell hypothesis is often criticised for its reliance on animal models of disease. Some researchers worry that the experiments used to identify putative cancer stem cells are too far removed from reality—human tumour cells do not naturally need to survive in mice—and thus may not reflect human cancer biology at all.
Proponents of the hypothesis are alive to that concern, but they think that the same pattern has been seen so often in so many different cancers that it is unlikely to be completely wrong. The practical test, though, will be whether the hypothesis and ideas that emanate from it, such as Dr Rich’s combination therapy, actually help patients survive.
Searching for the suspects
As a step towards discovering whether they do, William Matsui, an oncologist at Johns Hopkins University School of Medicine in Baltimore, looked for cancer stem cells in pancreatic-tumour samples taken from nearly 300 patients. His team found that patients whose tumours did contain such stem cells survived for an average of 14 months. Those whose tumours lacked them survived for 18 months.
That finding is consistent with the idea that cancer stem cells contribute to the most aggressive forms of the disease, though it does not prove they cause tumours in the first place. And although the absence of detectable stem cells in some tumours may be seen as casting doubt on the whole idea, it may instead be that they are too rare to be easily detected. If the stem-cell idea is confirmed, it may help doctors and patients choose how to treat different tumours. Those with detectable stem cells might be candidates for aggressive chemical and radiation therapies, while those without might best be treated with the surgeon’s knife alone.
Breast-cancer researchers are also testing the stem-cell hypothesis in the clinic. Jenny Chang’s group at Baylor College of Medicine, in Texas, took samples of tumours from women before and after standard chemotherapy. When they counted the cells in the tissue they found that the proportion of stem cells in a tumour increased after treatment. That suggests the chemotherapy was killing the non-stem tumour cells and leaving the stem cells behind. When the group repeated the experiment using a modern drug called Tykerb that blocks what is known as the HER2 pathway, they got a different result. HER2 is a gene which encodes a protein that acts as a receptor for molecules called growth factors which, as their name suggests, encourage cell growth and proliferation. After the HER2-blocking treatment, cancer stem cells formed the same proportion of the residual tumour as beforehand. That suggests they, too, were being clobbered by the new treatment. It is probably no coincidence that another drug, Herceptin, which also goes after HER2, is one of the few medicines that is able to prolong the lives of people with advanced cancer.
The stem-cell hypothesis has also changed the way people do basic research. For example, over the past few years cancer researchers have been grinding up pieces of tumour and using what are known as gene-expression microarrays to work out which genes are active in them. However, if the hypothesis is correct, this approach will probably yield the wrong result, because the crucial cells make up but a small part of a tumour’s bulk and the activity of their genes will be swamped by that of the genes of the more common non-stem cells. The answer is to isolate the stem cells before the grinding starts.
This approach has already yielded one important finding. When Dr Chang used microarrays to study gene expression in the CD44-positive cells from breast tumours, she noticed that they did not look like those of the epithelial cells that make up the bulk of such a tumour. Epithelial cells are immobile, grow in “cobblestone” patterns and produce proteins that help them stick together. The gene expression of the putative stem cells, however, resembled that of a mesenchymal cell. Mesenchymal cells rarely stick together. Indeed, they are mobile and are able to slip through the matrix of proteins that holds epithelial cells together.
That finding is important because mobile cells are more likely to escape from a tumour and form secondary cancers elsewhere in the body. Once such secondaries are established, successful treatment is much harder. And the CD44-positive cells also expressed genes that are important for stem-cell self-renewal, particularly one called Notch that controls the flow of chemical signals within a cell.
Researchers at OSI Pharmaceuticals, a firm that makes a drug called Tarceva, found a similar pattern in lung cancer. Several years ago, they started looking for gene-expression patterns that correlated with response to Tarceva. They found that tumours with a pattern that resembled epithelial cells were sensitive to the drug. By contrast, those that had a mesenchymal pattern were not. They hypothesised that as tumours develop, some of their cells actually switch from a sticky, epithelial state to a mobile, mesenchymal one. This epithelial-to-mesenchymal transition, or EMT, is well known to biologists who study embryonic development, but OSI’s results, and those of other researchers, suggest that cancers may have hijacked it for their own use.
Robert Weinberg, a molecular biologist at the Massachusetts Institute of Technology, and his colleagues have come to the same conclusion but they have taken the hypothesis one step further. They think that tumour cells which have undergone EMT have acquired many of the characteristics of cancer stem cells. Experiments in his laboratory, employing a variety of animal models of breast cancer, suggest that communication between tumour cells and surrounding non-cancerous support cells can lead some of the cancer cells to undergo EMT.
That is intriguing. If this transition really can be induced in tumour cells, then any of them might be able to become a cancer stem cell. So it may be that the fundamentalist version of the stem-cell hypothesis is wrong, and the stem cells are a result of a cancer, rather than its cause. That could be another reason why Dr Matsui found that pancreatic cancers do not always seem to contain stem cells.
Dr Weinberg is sensitive to this point, and is cautious when talking about these experiments. He refers to the cells that have undergone EMT as “having the qualities of stem cells” but avoids actually calling them cancer stem cells. If his idea is correct, though, it means that finding drugs which block the signals that induce EMT could reduce the stem-cell population and prolong the survival of the patient. It also means that both the epithelial cells and the mesenchymal ones will have to be attacked. And OSI is now testing a drug that does just that.
Notch up a victory?
Breast-cancer researchers, too, are testing drugs that hit molecular targets highlighted by cancer-stem-cell studies. Merck, for example, has turned to a drug it originally developed to treat Alzheimer’s disease. Although this drug, code-named MK0752, did not slow that disease, it does block activity of Notch, the stem-cell self-renewal gene, and might thus be an appropriate weapon against breast-cancer stem cells. Dr Chang and Dr Wicha have started a clinical trial which uses MK0752 in combination with standard chemotherapy. By the end of the year they hope to have some idea of whether the combination kills cancer cells in human tumours.
Attacking Notch is a high-risk approach, because this gene is used by healthy stem cells as well as cancerous ones; healthy organs as well as tumours could be damaged. Some researchers are therefore taking a different tack and looking for drugs that hit only the unhealthy stem cells. Craig Jordan, a biologist at the University of Rochester Medical Centre, in New York state, is one such. He has discovered that a chemical called parthenolide, found in feverfew, a medicinal plant, kills AML stem cells. Normal stem cells, however, seem to be able to tolerate the drug without difficulty. The reason is that the leukaemia cells are reliant on a biochemical pathway that parthenolide blocks, whereas normal stem cells are not. If all goes well, a trial to test the safety of a modified form of parthenolide will start in a few months.
If the safety issues can be dealt with—and most researchers think they can—then attacking cancer stem cells really could help patients survive. If, that is, the stem-cell hypothesis is correct.
At the moment, scientists being scientists, few are willing to be anything other than cautious. They have seen too many past cures for cancer vanish in a puff of smoke. The proof needs to come from patients—preferably with them living longer. But if the stem-cell hypothesis is indeed shown to be correct, it will have the great virtue of unifying and simplifying the understanding of what cancer is. And that alone is reason for hope.
Video: Actress & LC Survivor Kathryn Joosten on The View
in LUNG CANCER IN THE NEWS
Posted
What a wonderful way to kick-off Lung Cancer Awareness Month!
http://www.youtube.com/watch?v=GaDD1KbgHAg