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How Genomics Are Guiding Lung Cancer Patients Into Clinical Trials

How Genomics Are Guiding Lung Cancer Patients Into Clinical Trials

RECENT ADVANCEMENTS IN the treatment of lung cancer have significantly improved the length of time some patients are living. Where once lung cancer typically meant a life expectancy measured in just months, new targeted therapies are beginning to extend that timeline for some patients and offering many more months and maybe even years of life after diagnosis.

The term “targeted therapies” means these treatments are zeroing in on certain genetic mutations in the cancer cells and using them as a sort of self-destruct button to kill the tumor. They’re often superior to standard of care treatments like chemotherapy because rather than indiscriminately killing all quickly-dividing cells in the body – which causes the classic chemo side effects of nausea, vomiting and hair loss – targeted therapies take aim only at cells with those genetic mutations. This typically means fewer side effects and more precise cellular death.

The Memorial Sloan Kettering Cancer Center reports that “tumors in approximately 60 percent of patients with lung adenocarcinoma,” which accounts for about 40 percent of all cases of non-small cell lung cancer, “have been found to be linked to specific mutations.” These genetic mutations give rise to the development of the cancer, but increasingly also hold the key to slowing the tumor’s growth with advanced treatments.

But before a certain drug can be administered, your doctor needs to know whether your cancer has a genetic mutation that could be exploited, so you’ll need to undergo a detailed analysis of the tumor – a process called genomic testing. This testing can be carried out in a few ways, says Dr. Nathan Pennell, director of the lung cancer medical oncology program at the Cleveland Clinic’s Taussig Cancer Institute. “The gold standard for testing is still to test the actual tumor biopsy,” which entails taking a piece of tissue from the biopsied tumor and looking at it under a microscope. From there, scientists can “extract the DNA and possibly the RNA from the slide and then run the test on that.” (Genes are sections of DNA that tell the cell how to function, but it takes ribonucleic acid or RNA, to translate the instructions that DNA contains by creating proteins or carrying out other roles within the cell. RNA is essential in regulating the expression of genes.)

Another less invasive form of genetic testing can happen with a blood test, although the results aren’t as accurate as those gleaned from a tumor sample. “There are blood tests that can do this same testing because we know that cancer cells do die and release their DNA into the blood.” These tests are called liquid biopsies, and they may tell your doctor whether your cancer has a specific mutation, but “the major barrier to doing that has been the sensitivity of the test. It will never be as sensitive to find a genetic change in the blood as it is to find it in the actual cancer itself,” Pennell says, because there’s less of the cancer’s DNA in your blood than there is in the cancer cells themselves. Accuracy of liquid biopsies are “highly dependent on how good the test is. It also depends on how much cancer there is – so people who have a lot of cancer,” either a larger tumor or a later stage cancer, “are much more likely to have it detectable in the blood,” Pennell says.

The type of cancer can also impact the sensitivity of liquid biopsies. “Some cancers don’t shed as much DNA into the blood and so you may not find it.” All this means that a liquid biopsy might give you some good information about a cancer’s characteristics, but it often needs to be confirmed with a tumor biopsy. “You can’t trust a negative blood test for a genetic change,” Pennell says. “If you’re looking for something and you don’t find it in the blood, then you have to check it in the tumor itself. But if you do find it in the blood, it is trustworthy and you can use that.”

Depending on the test that’s being run, the pathologist may be looking for only a certain type of genetic mutation or several at once. “There’s what are called single gene tests where you’re looking for one thing, such as an EGFR mutation by itself,” Pennell says. (EGFR stands for epidermal growth factor receptor and refers to proteins on the cancer cells that bind with epidermal growth factor, a hormone in the body that cells use to grow. But because of a genetic mutation, some lung cancers have too many of the receptors for this hormone, and the tumor uses the excess EGF to fuel its growth.)

EGFR has gotten a lot of attention lately for breakthrough treatments that have recently been developed, but it’s not the only genetic mutation that doctors are using to treat lung cancer. Other terms you may hear include ALK, RET, ROS1 and BRAF, all different kinds of genetic mutations targeted by newer drugs and therapies currently being tested in trials. Therefore, some tests use a technique called next-generation sequencing to look for all known mutations. “The way the field is moving is to do a single, broad NGS-based test that will look at all the known cancer related genes,” Pennell says. “You can get that result within a couple of weeks so that you can use it to treat the patient and/or offer them a clinical trial.”

Dr. David P. Carbone, director of the Thoracic Center and professor of medicine at the Ohio State University James Cancer Hospital in Columbus, says genomic testing for lung cancer is looking for a different type of mutation than is implicated in some other kinds of cancer, such as the mutations on the BRCA1 or BRCA2 genes that are linked to breast cancer. “The BRCA gene testing for breast cancer is a test for an inherited susceptibility gene,” he says. But for the kind of lung cancer mutations we’re talking about here, the test is looking for genetic changes that aren’t inherited, but have been switched on at some point during the patient’s life. “The genetic testing I’m talking about is for damage to genes that are in your cancer but not in the rest of your body and not inherited by your kids. But they do inform the types of treatments that you’ll get.”

And this is where the genomic testing rubber meets the road: by helping doctors match patients with the best treatment for their individual cancer – an approach often referred to as personalized medicine. Testing for known genetic mutations means patients might become eligible for new or experimental drugs that could offer a better prognosis than more traditional treatments such as chemotherapy, radiation and surgery.

“It’s an important point to stress that people should be getting genetic testing at the time of diagnosis for lung cancer so that the optimal treatment can be selected,” Carbone says. But “many people still don’t do that. It’s recommended to be [part of the standard of care] but it doesn’t happen in everybody,” he says. If your doctor doesn’t automatically test your cancer for genetic mutations upon diagnosis, ask why not and consider seeking a second opinion.

When you are tested, the results may mean you’ll be eligible to take part in a clinical trial for a new therapy. These research studies help determine the safety and efficacy of new drugs or therapies and are an important step in the process of bringing new treatments to market for every disease. The American Cancer Society reports that clinical trials can leave the patient with some feelings of uncertainty, but they may also offer a better alternative to the current standard of care. “Part of it is that the doctors in charge of a clinical trial don’t know ahead of time how things will turn out. If they did, there would be no need for the study in the first place.” But clinical trials are how we learn what works, and the patients who volunteer to help researchers are helping advance our understanding of cancer and its management.

“I think clinical trials should be part of our standard of care,” Pennell says. “Clinical trials are really revolutionizing treatment for many patients now. They’re a lot more rational than they used to be,” he says noting that in the past, “you’d have a clinical trial of a drug and you’d give it to every type of cancer patient and it only worked in a few of them or none of them. But these days we have a much better idea before we even start the clinical trial who’s likely to benefit,” which may lead to better outcomes.

And once a clinical trial for a certain drug has concluded, sometimes it earns approval from the FDA to become an accepted and much more widely available treatment for other patients with that same disease.

“I would highlight that this is no longer experimental,” Pennell says. “This is no longer something that’s coming in the near future. This is here. Genomic testing for lung cancer and for other types of cancer is already here. We already have approved and available drugs that are prolonging people’s lives based on these tests. Everyone who has cancer should ask their doctor if it’s part of their workup and treatment, especially if you have lung cancer. That’s absolutely the standard of care to do that,” he says.

Source:- usnews
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