Genomics + Prostate Cancer

In April, Prostatepedia is talking about how genomics is impacting prostate cancer treatment.

Dr. Snuffy Myers offers his thoughts on genomics and on this month’s conversations.

I am especially excited about our April issue. Genomics offers multiple ways to improve prostate cancer treatment. We are only at the beginning of the genomics revolution.

I am well aware, though, that many of our readers may not have a sufficient scientific background to fully understand the power of this way of looking at cancer.

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The key insight is that gene expression determines a cancer cell’s behavior. Before the genomics revolution, we tried to predict cancer behavior based on appearance under the microscope—i.e. Gleason grade or imaging techniques. This approach has had its successes but is far from perfect. Instead of inferring behavior from appearances, genomics looks directly at the genes that drive behavior.

Genomics for prostate cancer is most advanced for newly diagnosed low to intermediate risk disease. We have several competing commercial products; the three most widely used are Decipher, Oncotype, and Prolaris. All three look at the expression of multiple genes. The pattern of expression of these genes has been shown to correlate with a cancer’s future behavior.

I have been particularly interested in a next generation test called the Decipher Grid. It dramatically expands the number of potentially important genes tested. This includes genes that may predict responsiveness to radiation, hormonal therapy, and some chemotherapy agents. Time will show Decipher’s Grid’s usefulness.

When a specific gene mutation is known to drive the growth of a cancer, it is possible to develop drugs that selectively kill cancer cells that have that mutation. This process has already revolutionized lung cancer treatment. For prostate cancer, we now have only a few examples. In several conversations this month, doctors mention DNA repair mutations BRCA2 and ATM. These mutations are commonly linked to breast and ovarian cancer. A class of drugs called the PARP inhibitors are effective treatments for ovarian and (to a lesser extent) breast cancers containing these mutations. When these mutations are inherited, they are associated also with an increased risk of aggressive prostate cancer.

While the frequency of BRCA2 mutations is low at diagnosis, the incidence increases as prostate cancer advances. Several studies show that 25-35% of advanced prostate cancers contain mutant BRCA2 or ATM. One Phase II clinical trial reported a greater than 80% response to a PARP inhibitor. Other genes important in aggressive prostate cancer include TP53, PTEN, and RB1. However, no drugs are clinically available to target cells where the function of these genes has been altered or eliminated. TP53 and PTEN have selective drugs in preclinical and clinical testing. The take-home message is that genomics is already improving the treatment of newly diagnosed prostate cancer and offers hope for better treatments for advanced disease.

Subscribe to read our April issue on genomics.

(Subscribers, you can read all conversations about genomics in your April issue of Prostatepedia.)

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