How Genetic Testing Can Guide Cancer Treatment

April 10, 2019 US News & World Report

IF YOU KNOW EVEN A little about the biology of cancer, then you know that cancer is a genetic disease. All cancers are caused by damaged genes, typically a handful of changes in a person's DNA that result in runaway cell growth.

Human beings have roughly 20,000 genes, and many cancer discoveries over the past couple of decades have involved identifying the specific gene alterations, often mutations, that lead to various types of malignancies such as bone, prostate and breast cancer as well as blood cancers like leukemia.

The good news: After decades of painstaking progress, scientists are rapidly learning about the genetics of cancer and what causes healthy cells to go rogue. The result is a revolution of new treatments.

Cancer treatment traditionally means some combination of surgery, radiation and chemotherapy. As an oncologist, I can attest that these traditional therapies can be effective, but because both chemotherapy and radiation affect healthy cells as well as cancerous ones, these therapies can also come with unwelcome side effects. Many patients lose their hair and become nauseated when undergoing chemotherapy, for example.

Now, thanks to what we are learning about genes and cancer, oncologists like me often can offer patients novel treatments based on the genetics of their individual disease. These new drugs and therapies can work better to eliminate the cancer, with lesser side effects. This is why genetic testing can be so beneficial for cancer treatment.

Cancer is also highly individual: It can vary by the person as well the type. One man's stage 2 prostate cancer is not identical to another man's stage 2 prostate cancer. Today, by running tests to find a cancer patient's individual genetics, I can potentially find a treatment targeted to that patient's abnormality.

What kind of genetic testing is used for cancer treatment?

First, let me clarify what kind of genetic testing is used for cancer treatment. People often assume "genetic" means "inherited" because our genes come from our parents. Some genetic abnormalities are indeed inherited; e.g., the BRCA gene that leads to breast cancer. Some people with a family history of a certain kind of cancer opt to be tested for inherited mutations to learn if they are at increased risk for the disease. This kind of screening is typically a blood test conducted by clinical geneticists.

But inherited mutations account for only 5 percent of cancers. The remaining 95 percent are caused by genetic mutations that happen spontaneously, likely because of age or environmental factors such as cigarette smoke. We test for these acquired mutations in the cancer itself, by running a genetic test on a tumor specimen, in our pathology department or an outside lab. With few exceptions, it is these sudden mutations, not the inherited kind, for which we have new treatments.

Another important take-away: If you have cancer and your tumor is found to have a certain mutation, in most cases you do not need to fear that your children will inherit it or that your sister has it also. The mutation is located in your cancer only.

Targeted therapies

For most cancers, we look for mutations in the cancer for which we have related drugs known as targeted therapies.

Targeted therapies typically attack processes unique to the growth of cancer cells. These processes often involve proteins. Genes produce proteins that do the work of the cell. Often, when we test for genetic abnormalities, we find them by discovering abnormally high levels of the related protein, or altered protein activity.

There are dozens of targeted therapies to treat many different types of cancers, but here a few examples:

Imatinib, approved by the Food and Drug Administration in 2001, treats chronic myeloid leukemia and was the first targeted cancer therapy. Taken orally, Imatinib attacks a protein produced by an abnormal gene that causes leukemia cells to grow and reproduce uncontrollably. It has improved the survival rate from under 30 percent to over 80 percent, while enabling patients to be treated at home by taking a pill and subjecting them to fewer side effects.

Patients with breast cancer are often regularly tested for high levels of the HER2/neu protein, which accelerates the growth of cancer cells. If they test positive, they might be a candidate for trastuzumab, which shuts down the protein.

At the end of last year, the FDA approved larotrectinib, a drug that treats solid tumor cancers of any type (e.g., thyroid, lung) in people who test positive for an altered NTRK gene that helps cancer grow. This is the first targeted therapy that can treat cancer irrespective of its location in the body.


In the past five years or so, another new class of cancer drugs, immunotherapies, have shown huge promise. With these drugs, we are not targeting mutations but are trying to put the immune system into overdrive so that it recognizes cancer and fights it. For years, we didn't think immunotherapy was possible for cancer because cancer comes from a person's own body and the immune system therefore would not be able to distinguish it as something foreign.

But we found that immunotherapy can work in some cancers with many mutations, such as in smoking-related cancers like lung and bladder cancer. We test the malignancy for a genetic issue known as microsatellite instability, which is an indicator of a cell's ability to repair itself when DNA becomes damaged. If your cancer tests positive for microsatellite instability, you might be a good candidate for an immunotherapy.

Immunotherapies can treat many types of cancer. And in 2017, the FDA approved the first cancer immunotherapy based solely on genetics and not the type of tissue or location of the cancer: pembrolizumab, which blocks a pathway that enables cancer cells to hide from the immune system.

Next generation genetic sequencing

On the horizon is next generation genetic sequencing. It's similar to consumer genetic tests that people do through the mail, but can be done on cancer specimens. It looks for many, many different actionable targets at once.

At Mid-Atlantic Permanente Medical Group, we will be participating in a clinical trial that uses next generation sequencing for stage 4 cancers. We will take specimens from our participating patients and sequence them for 100 targets. For these patients in the late stages of the disease who don't have much time to try different therapies, searching for so many targets at once could offer a better chance of finding a new therapy suited to their individual cancer.

I've barely scratched the surface of what is happening in the field of genetically-based cancer treatment, and new findings are made daily. If you're facing a cancer diagnosis, be sure to talk to your doctor about how genetic testing could help you find the best treatment.

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