The Cancer Genome Atlas (TCGA) made a big splash in the media recently with a publication in the scientific journal Nature, "Comprehensive molecular portraits of human breast cancer." What many news media outlets picked up on was the molecular similarity between ovarian cancer and a particularly difficult-to treat subtype of breast cancer termed triple-negative breast cancer. The research suggested that triple-negative breast cancer patients may benefit from treatments commonly used in ovarian cancer. This promising finding for triple-negative breast cancer patients was what the media was buzzing about. But the really important story is that TCGA is putting together the molecular maps for twenty different cancer types. An atlas, after all is a collection of maps. This atlas will be able to inform treatment decisions based on a tumors molecular geography rather than its anatomic geography, what tumors look like at the molecular level rather than where in the body the tumor originated.

 

Looking at a tumor's molecular profile may suggest a more rational and effective treatment plan. An example of how TCGA has advanced this new vision for cancer treatment comes from its completed molecular map of ovarian cancer. The TCGA study found that that ~35% of ovarian cancers have alterations in a pathway known as PI3K/AKT and another ~10% in the RAS-MAPK pathway which are key regulators of cancer cell growth. Ovarian cancer patients with mutations or potential defects in these pathways are being matched with drugs developed to target those pathways in a number of clinical trials.

 

Dr. Douglas Levine, Head of the Gynecology Research Laboratory at Memorial Sloan-Kettering Cancer Center and Clearity Foundation Scientific Advisory Board member writes, "I hope to see genomics-directed trials that are somewhat agnostic to tumor site of origin after further proof of principle studies help to turn this admirable goal into reality."   >> Read Dr. Levine's perspective

 

Clearity is committed to helping ovarian cancer patients find out which genomic alterations are found in their tumors so that they may benefit from investigational drugs that target the specific pathways that have been activated by those mutations. To enable this, we have recently begun to offer a testing panel that measures mutations in some of the genes identified in the TCGA ovarian cancer study. Since mutations in many of these genes are linked to drugs being tested in clinical trials, we hope that this knowledge will help patients and their physicians make informed choices about which clinical trial drugs could provide them the most benefit. To learn more about these mutations, pathways, associated drugs and the clinical trials that are testing them, please watch for our series of articles on "Clinical Trials-Why Now?" to be published in future newsletters.    Deborah Zajchowski, PhD 

 

The Clearity Foundation is entering our 5th year of providing tumor blueprints to women battling ovarian cancer to improve their treatment options.  I would like to thank each of you for your participation.  When we launched Clearity with our first profiles in 2008, we knew that we would need an "evergreen" process.  As more has become known about the alterations that drive response to chemotherapy or resistance to treatment, Clearity has added additional tests to the panel.  We work closely with the CLIA-certified laboratories so that the latest tests can be brought to you.  We have been offering a broad mutational panel with Foundation Medicine since early this year.  While we have not been able to obtain this information on everyone due to limitations on sample size, we have now completed enough cases to know that this can be helpful in selecting among clinical trial options.  Together with the chemosensitivity and chemoresistance panels that are conducted at Caris Life Sciences and Clarient, Inc., the Clearity Foundation brings to women with ovarian cancer the most comprehensive testing available.  Our mission is to help every woman battling ovarian cancer get the right drug for her which we believe will not only change the paradigm for treatment but ultimately provide more cures.     Laura Shawver, PhD

Like our ambition to reach Mars, completion of the Cancer Genome Atlas for all twenty cancers is not just a destination, but also a journey. This journey has already begun to alter perceptions on how we think about cancer treatment. The work from these maps supports Clearity's approach to molecularly profile ovarian tumors. This profile gives patients and their physicians an idea of where on the molecular map a tumor is situated and what treatment options are suggested by this geography.