ON the Horizon this year

[Elaine]

Excerpt from Wall Street Journal Jan 26, 2004

Looks like some things that may benefit LC--even though the research was done with Breast Cancer--go figure.

Cancer Prediction

Cancer researchers are making strides on several fronts this year to better predict how certain cancers will grow and which patients need the most aggressive treatments.

At the University of Texas M.D. Anderson Cancer Center in Houston, several new molecular-imaging machines will allow doctors to find out far sooner whether a particular cancer treatment is working.

In the past, patients had to endure weeks of chemotherapy or other drugs before they and their doctors could find out whether a given treatment was actually shrinking a tumor. But the new imaging methods will allow doctors to gauge the efficacy of a particular treatment far sooner by studying changes in the tumor that are evident long before it would typically start to change in size. In patients with a rare form of abdominal cancer, for instance, doctors can use molecular imaging to discern within just 24 hours whether the targeted therapy Gleevec will be effective.

For patients, the breakthrough means they don't have to undergo weeks of toxic treatments only to learn the therapy was a waste of precious time. For doctors, the molecular images give a far more detailed understanding of the tumor, and open the door for a number of promising new treatments.

"Think how many lives we can save with this, how many ineffective therapies we can drop and try to do something else with the patient," says Juri Gelovani, chairman of the department of experimental diagnostic imaging at M.D. Anderson. "It will have an immense socioeconomic impact."

And as early as March, CellSearch, a new blood test from Johnson & Johnson, will be made available to the research community as the company awaits FDA approval, expected later this year. CellSearch is a simple blood test capable of detecting minuscule amounts of tumor cells circulating in the blood. Knowing whether circulating tumor cells are present helps doctors predict whether they need to offer a more aggressive treatment.

The test has been studied in patients with advanced breast cancer, but its most important use probably will be in women with early-stage breast cancer. In women diagnosed with early stage cancer, as many as 30% will suffer a relapse -- probably because conventional diagnostic methods failed to detect that their cancer had already spread. The test may also ultimately be used to better predict whether cancer has spread in patients with prostate or colorectal cancer.

And a study released in December has prompted widespread interest in "molecular profiling" of cancer -- using genes and proteins associated with cancer to better predict just how aggressive the tumors will be. In a Dutch study, the technique gave far more accurate predictions of survival rates among 3,000 breast-cancer patients than traditional methods. The report has triggered a wave of new research being put into practice at medical research centers around the country. Researchers at Vanderbilt University's School of Medicine this summer will begin studying a profile that should help predict which patients will benefit from Iressa, a lung cancer drug.

"This information tells you from the beginning what's going to happen to that patient," says David H. Johnson, deputy director of the Vanderbilt-Ingram Cancer Center and president-elect of the American Society for Clinical Oncology. "It tells you the behavior of the cancer, and it gives you the destiny of that tumor."

[gpawelski]

Cleveland Clinic Recognizes Circulating Tumor Cell Technology As Top Medical Innovation For 2009

Veridex, LLC announced that the technology used in the CellSearch System to measure circulating tumor cells (CTCs) was ranked as the top medical innovation for 2009 by the Cleveland Clinic, a leading multispecialty academic medical center. The ranking is based on technologies likely to have a significant impact on health care next year.

The prestigious annual recognition follows a rigorous selection process by a panel of Cleveland Clinic physicians. The list was announced today at the Cleveland Clinic's 2008 Innovation Summit.

http://www.medicalnewstoday.com/articles/129501.php

[gpawelski]

Results of using the CellSearch System indicate that monitoring of circulating tumor cells (CTC's) can contribute to the understanding of tumor-blood interactions and may provide a valuable tool for therapy monitoring in solid tumors like breast, colorectal or prostate cancer. With cells being alive in circulation, it may mean that a patient would need additional treatment.

These ciculating tumor cells can detach from solid tumors and enter the blood stream, thus beginning the process of metastasis, the most life-threatening aspect of cancer. To metastasize, or spread cancer to other sites in the body, circulating tumor cells travel through the blood and can take root in another tissue or organ (like the lungs, bones, liver, adrenals and even the brain).

Immunicon's founder/scientist (immunologist) Paul Liberti's Immunicon team developed all the technology to help researchers and oncologists monitor CTC's. Immunicon licensed their technology to Johnson & Johnson who formed a new unit called Veridex to market Immunicon's CellSearch technology. The technology gives the patient and oncology community a great method to monitor treatment.

The CellSearch system can be very complimentary to an array of tools that oncologists should be using to counsel their patients. The technique can be done earlier than other currently approved diagnostic modalities like CT, MRI or PET imaging. CellSearch is basically what is going on with functional profiling, which shows what patients are benefiting from what drug agents "before" introducing them into the patient.

Anti-cancer treatments often effectively shrink the size of tumors, but some might have an opposite effect, actually expanding the small population of cancer stem cells believed to drive the disease. Some treatments could be producing more cancer stem cells which are then capable of metastasizing, because these cells are trying to find a way to survive the therapy. The tumor escapes from chemotherapy by induction of stem cell marker expression. The small number of cells that survive the treatment could then generate another tumor that metastasizes.

This may help explain why the expression of stem cell markers has been associated with resistance to chemotherapy and radiation treatments and poor outcome for patients with cancers including prostate, breast and lung cancers. That tells us that understanding how to target these markers and these cells could prove useful in treating these cancers.

Analysis of stem cell expression before and after treatment reveals that even as some anti-cancer treatments shrank tumors, they increased expression of stem cell markers (of which contibute to stem cells' defining ability to renew themselves and differentiate into different cell types). Some treatments are not enough to completely inhibit tumor growth, and the cancer stem cell markers are still present.

Even if one or more chemotherapy regimen is identified as being likely to work on a particular cancer, has the science advanced to tell us whether application of the chosen chemotherapy regimen will not cause other changes that also cause cancer to later return and perhaps be even harder to treat? Is it a case of chemotherapy being bad, in cases where it apparently works? Chemotherapy can be mutagenic (changes in form). It might kill off a whole lot of cancer, only to cause a mutation in the remaining cancer, such that the remaining cancer behaves in a more aggressive fashion.

Much more work needs to be done, and oncologists need to adapt treatment to the patient. There are hundreds of chemotherapeutic agents, all of which have approximately the same probability of working. The tumors of different patients have different responses to chemotherapy. It requires individualized treatment based on testing individual properties of each patient's cancer.

Sources:

BMJ2007;334(suppl 1):s1(6January),doi:10.1136/bmj.39034.719942.94

The European Science Foundation

Cell Function Analysis

journal Molecular Biology of the Cell

American Assoication for Cancer Research