Personalized Medicine for Colon Cancer: New discovery helps doctors accurately predict which patients will be helped by certain drugs

Personalized medicine—where doctors tailor treatment of a disease to characteristics of an individual person and unique features of his or her disease —is becoming a reality for colon cancer patients. Some recent discoveries offer incredible new insights that may help physicians better select treatments for specific patients.

One way scientists study personalized medicine is to look at the specific and unique abnormalities in a patient’s cancer cells. While two people may have the same type of cancer, certain genetic aspects of their tumor cells may be different.  Treatments are then designed to work off of these differences. For example, let’s assume that a specific chemical reaction is needed for a specific person’s cancer cell to grow. If we can make a drug that interferes with that chemical reaction, there is a good chance that we can interfere with the cancer cell’s growth—and potentially improve the patient’s cancer.

There are many different ways that colon cancer can be stimulated to grow. On the surface of colon cancer cells are substances called receptors—things that look like mini locks. Our blood contains some chemicals (called growth factors) that can interact with these receptors—sort of like keys that fit into the locks. When a receptor and its matching growth factor come together, the cancer gets turned on, and this sets in motion a series of chemical reactions that allow it to grow and do all the bad things that cancer cells do.

One specific class of drug—called growth factor blockers—can interfere with this lock and key interaction, and thereby interfere with the signals that allow the colon cancer cells to grow. Several recently completed clinical studies have shown that about 40% to 50% of patients with colon cancer respond well to these drugs. But the big news came when researches looked more carefully at the cancers and tried to distinguish if there were any differences in the chemical make up of the cancer cells (so called molecular characteristics) that responded positively to the treatment versus the ones that didn’t. And what they discovered is profound.

There is a substance in all of the body’s cells—including cancer cells—called Kras. Cancers that responded well to growth factor blockers had a form of Kras that looked pretty much like Kras of normal cells. In the cancer cells that did not respond well, the Kras was altered and mutated and unlike that found naturally.

It turns out that a normal form of Kras is needed for the growth factor blocker to stop the growth of colon cancer. If Kras is mutated, the growth factor blocker simply does not work. There are ways to test people to see if their cancer cells have a normal or abnormal form of Kras, so we can now predict if a growth factor blocker would work based upon this test.

Why is this discovery so important? There are several reasons:

• First, growth factor blockers have a spectrum of side effects such as skin reactions, abdominal pain, infusion reactions, diarrhea, and scarring of the lungs.

So your doctor would not want to prescribe the drug if there was little likelihood of it working.

• Second, greater hope can be offered to patients if they have a normal form of Kras and are given the drug.

• Third, these drugs are expensive. There would be no reason to prescribe an expensive drug to a patient whose cancer has an abnormal form of Kras, where the probability of it working is small to non-existent. National cancer organizations have recommended that insurers require Kras testing, so that insurers can decrease unnecessary spending on these drugs in people for whom they will not work.

I predict that in the very near future, additional research on the specific molecular characteristics and chemical processes of tumor cells will be discovered in other types of cancers. This will lead to the development of specific drugs that interfere with these reactions. Further research will then be directed into getting a better understanding of the differences in those patients whose cancers respond favorably and those that do not.  Already, this is happening in patients who have a specific type of non-small cell lung cancer.  No doubt, it will be applied to other cancers soon.

Marc Garnick, M.D., is an internationally renowned expert in medical oncology and urologic cancer, with a special emphasis on prostate cancer. He is a Clinical Professor of Medicine at Harvard Medical School and maintains an active oncology practice at Beth Israel Deaconess Medical Center. Dr. Garnick serves as Editor in Chief of Perspectives on Prostate Diseases, a quarterly report from Harvard Health Publications.

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