Genetic Testing for People with Lung Cancer
Understanding Molecular Profiling
By Lynne Eldridge MD
Updated March 31, 2014
Written or reviewed by a board-certified physician.
Gene Mutations in Lung Cancer
One of the most exciting advances in the treatment of lung cancer has come from an understanding of genetic changes in lung cancer cells. Whereas in the past we broke lung cancers down into perhaps 5 types, we now know that no two lung cancers are the same. If there were 30 people in a room with lung cancer, they would have 30 different and unique types of lung cancer.
If you’ve been recently diagnosed with lung cancer, especially lung adenocarcinoma, your oncologist may have talked to you about genetic testing (otherwise known as molecular profiling or biomarker testing) of your tumor. It's now recommended that all lung cancer patients with advanced or metastatic lung adenocarcinoma (a type of non-small cell lung cancer) have biomarker testing to look for EGFR mutations and ALK rearrangements. In addition, non-smokers with other forms of non-small cell lung cancer should be considered for testing. What does this mean?
What is Genetic Testing (Molecular Profiling) of a Lung Cancer Tumor?
Genetic testing involves tests that a pathologist performs in the lab using a sample of your cancer tissue - tests that look at the cancer from a molecular level. This tissue may come from a biopsy of your tumor, or from tissue removed during surgery for lung cancer. The reason behind this is that cancers have gene mutations that "drive" or control the growth of the cancer. Simplistically, if these mutations can be identified, then treatments can be used which "target" these mutations, hence stopping the growth of the cancer. It is these mutations (usually a minimum of 6 or 7) that lead to the development of a cancer in the first place.
Before going further it's helpful to address something that is confusing for many people. There are two primary types of gene mutations.
Hereditary Mutations vs Aquired Mutations in Cancer
One type of mutations are hereditary mutations (also called germline mutations,) meaning you inherit genes with mutations from one or more parents. Common examples of these mutations include hemophilia, as well as mutations that may predispose someone to developing breast cancer (BRCA1 and BRCA2 mutations.)
The type of mutations that scientists look for in people with lung cancer are instead called acquired mutations (also called somatic mutations.) These mutations are not present at birth (they do not run in families) but rather develop in the process of cells becoming cancerous.
What are Cancer Cells?
Cancer Cells vs Normal Cells
What Exactly are Gene Mutations?
Gene mutations are changes to a particular gene in a chromosome. All genes are made up of 4 amino acids (called bases); adenine, tyrosine, cytosine, and guanine. When a gene is exposed to toxins in the environment, or when an accident occurs in cell division, a mutation (change) may occur. In some cases it may mean that one base is substituted for another, say adenine instead of guanine. In other cases bases may be inserted, or deleted, or genes may be rearranged in some way.
Significance of Gene Mutations
Why are oncologists interested in acquired gene mutations in a tumor? First, we should talk about the two types of acquired mutations found in lung cancers. One type of mutation is termed a driver mutation. These mutations, via several mechanisms, “drive” the growth of a tumor. It’s not known exactly how many driver mutations are present in a cancer, but estimates suggest around 1 to 10 are present in most cancers. Another type of mutation is termed a passenger mutation. Just as someone may be a passenger in a car, these genes do not drive the cancer and are basically along for the ride. Again we don’t know exactly how many passenger mutations are present in a tumor (and the number varies from tumor to tumor) but some tumors may have upwards of 100,000 passenger mutations. Interestingly some passenger mutations may actually retard the growth of a tumor.
Driver mutations not only initiate the development of a cancer, but work to maintain the growth of a cancer as well.
Common Driver Mutations Found in Lung Cancer Tumors
There are many mutations that are being studied by scientists looking at lung tumors. So far driver mutations have been found in 62% of lung adenocarcinomas. Researchers are now finding driver mutations in squamous cell lung cancer as well.
Common driver mutations in lung cancer include (for starters):
EGFR mutations
KRAS mutations
EML4-ALK Rearrangements
MET signaling
Personalized Treatments Available Based on Genetic Testing
The use of "targeted therapies" - that is medications that target particular genetic abnormalities in a tumor -- has been coined personalized medicine. What this means is that rather than a conventional chemotherapy drug that attacks all rapidly dividing cells, a targeted drug instead attacks a particular abnormality present only in cancer cells. In general targeted treatments have fewer side effects than traditional chemotherapy. To date, targeted therapies that have been approved for people with lung cancer include:
Tarceva (erlotonib) has been approved for people whose tumor has an EGFR mutation (note: there are different types of EGFR mutations)
Xalkori (crizotonib) was approved by the FDA in 2011 for people whose tumor has an ALK4-EML gene rearrangement
Other medications are being studied in clinical trials, including targeted therapies for those whose tumor becomes resistant to Tarceva or Xalkori..
A challenging problem with current treatments is that nearly everyone inevitably becomes resistant to treatments we have. There are many mechanisms by which this occurs making it difficult to find one solution. Research is ongoing in clinical trials; evaluating both the use of substituting a second drug to target the mutations, and drugs that address problems with resistance directly.
The Future
The ability to understand the molecular profile of lung tumors is an extremely exciting area of research, and it’s likely that new treatments for other mutations will soon be available. An example of how rapidly this area of medicine is advancing is the ALK4-EML gene rearrangment. This gene "mutation" (actually a rearranglement) was discovered as recently as 2007. Through a rapid process, the medication Xalkori (crizotinib) was approved in 2011 for general use by the FDA for those patients whose tumors have this rearrangment. There are clinical trials currently in progress evaluating the use of second generation drugs for those who have become resistant to Xalkori.
Next Step
If you have been diagnosed with non-small cell lung cancer, especially lung adenocarcinoma or squamous cell lung cancer, talk to your doctor about genetic testing. Although testing is now recommended for everyone with non-small cell lung cancer, a recent study reported that only 60% of oncologists are currently ordering testing. You may also wish to talk to your doctor about clinical trials that may be an option for you. If you are interested in looking into trials evaluating these treatments worldwide, check out the article below on how to find clinical trials. It can be confusing as you check out these databases, but help is near. Recently a lung cancer clinical trial matching service backed by several lung cancer organizations has become available. With this free service a trained nurse navigator can help you locate any clinical trials that may be an option for you.
Sources:
Hensing, T., Chawla, A., Batra, R., and R. Salgia. A personalized treatment for lung cancer: molecular pathways, targeted therapies, and genomic characterization. Advances in Experimental Medicine and Biology. 2014. 799:85-117.
Kim, H., Mitsudomi, T., Soo, R., and B. Cho. Personalized therapy on the horizon for squamous cell carcinoma of the lung. Lung Cancer. 2013. 80(3):249-55.
Li, T., Kung, H., Mack, P., and D. Gandara. Genotyping and genomic profiling of non-small-cell lung cancer: implications for current and future therapies. Journal of Clinical Oncology. 2013. 31(:1039-49.
Luo, S., and D. Lam. Oncogenic driver mutations in lung cancer. Translational Respiratory Medicine. 2013. 1:6.
Villaruz, L., Burns, T., Ramfidis, V., and M. Socinski. Personalizing therapy in advanced non-small cell lung cancer. Seminars in Respiratory and Critical Care Medicine. 2013. 34(6):822-36.
http://lungcancer.about.com/od/Targeted ... Cancer.htm
By Laura Nathan-Garner on June 18, 2014 7:30 AM | Neuropathy For many of our patients, peripheral neuropathy is among the unexpected side effects of cancer treatment. It's caused by damage to your peripheral nerves -- that is, the nerves that are farther away from your brain and spinal cord. Certain complications of cancer or cancer treatments can cause or worsen neuropathy. So can some health conditions, such as diabetes, alcoholism, AIDS, hypothyroidism, rheumatoid arthritis and carpel tunnel syndrome. We recently spoke with Julie Walker, advanced practice nurse in Neuro-Oncology, about peripheral neuropathy. Here's what she had to say. What causes peripheral neuropathy in cancer patients? The nerve damage that causes peripheral neuropathy may be the result of many different factors, including some chemotherapy drugs using vinca alkaloids, platinum compounds, taxanes and thalidomide. Tumors themselves can cause nerve damage as well if they grow close to and press on the nerve. And, patients with cancers of the nervous system -- such as brain tumors, spine tumors and skill base tumors -- are more likely to develop peripheral neuropathy due to nerve damage resulting from the tumor. What are common peripheral neuropathy symptoms? Symptoms depend on the type(s) and location(s) of the damaged nerves. The most common peripheral neuropathy symptoms include: numbness tingling shooting pain or burning, especially in your fingers or toes. Other peripheral neuropathy symptoms include: loss of balance, difficulty walking or frequent falls clumsiness difficulty picking up objects or buttoning your clothes facial pain hearing loss loss of sensitivity to hot and cold stomach pain constipation What can cancer patients do to relieve peripheral neuropathy? If the neuropathy is related to something you can control, try to control the cause. If your neuropathy is chemo-related, your oncologist can decide whether it's beneficial to reduce your chemotherapy dosage or switch to a different treatment regimen. If it's related to diabetes, you can often slow down or stop the progression of peripheral neuropathy with better blood sugar control. Beyond that, physical activity can help by keeping blood flowing in the affected areas. Some people also try acupuncture. Over-the-counter pain relievers and prescription medications like carbamazepine and Lyrica may help in some cases. Non-prescription-type treatments -- such as acetyl l-carnitine, alpha lipoic acid, glutamin, calcium and magnesium -- may help, too. But more research is needed to better gauge their effectiveness. Be sure to speak with your health care provider before trying any of these. What can cancer patients do to lower their chances of developing peripheral neuropathy? If you have other health conditions, such as diabetes, that can make the neuropathy worse, manage them appropriately. Limit alcohol use. Maintain a well-balanced diet. And, discuss your neuropathy risks with your health care provider. How long do peripheral neuropathy symptoms last? Every case is different. Because neuropathy is caused by nerve damage, it depends largely on how well your nerves recover. And, that depends on the length of your treatment, extent of the damage and, in the case of chemotherapy-induced neuropathy, dosage intensity. It's usually possible to manage peripheral neuropathy up to a certain point, but for many people, it never goes away. As the nerves heal, some people may actually experience more tingling in the affected area. Speak with your health care provider to find out if a prescription might help relieve symptoms during this time. People with peripheral neuropathy lose the ability to feel pain or extreme temperatures in the affected areas. What can cancer patients with peripheral neuropathy do to avoid burning or injuring themselves? Always wear shoes to protect your feet from an injury. Also, make sure you examine your feet every day to look for any wounds or sores that aren't healing. Be careful when using sharp utensils or avoid them altogether. Likewise, since neuropathy typically inhibits your fine motor movements, be cautious around or avoid dangerous machinery. Before touching water with your hands or feet, feel the water with a part of your body -- such as the underside of your forearm -- that can sense how warm it is. And, avoid using heating pads and hot water bottles. Any other advice for cancer patients who are experiencing neuropathy? People with neuropathy are more prone to falls because they struggle to feel the ground beneath them, especially in the dark or an enclosed space. So: use a nightlight keep clutter and throw rugs off the floor use handrails when taking the stairs put handrails in the shower use skid-free shower and bath mats Neuropathy also makes the body more prone to infection since circulation is decreased and wounds don't heal as well. So it's a good idea to keep your skin moist to prevent cracking and, in turn, infection. The most important thing you can do, though, is to speak with your health care provider as soon as you start to experience neuropathy symptoms. Together, you can hopefully find ways to manage your symptoms. http://www2.mdanderson.org/cancerwise/2 ... ients.html