Towards Personalized Medicine in Ovarian Cancer

The goal of personalized medicine remains in its infancy as oncologists strive to determine treatments specific to a patient's tumor characteristics. Indeed, it is a goal as we move in to the future to individualize treatment paradigms, so as to maximize treatment success and avoid exposing patients to treatments that were pre-determined not to be effective.

Still, the tools to allow us to do so are crude and not fully available. In addition, our understanding of tumor heterogeneity seems to continue to expand and become ever more complicated, marking the realization that "personalized" treatment plans would require far more sophisticated trial designs that have yet to be employed even at the best centers.

In ovarian cancer results coming out of the Cancer Genome Atlas illustrate this heterogeneity within serous types of ovarian cancer. Utilizing individual tumor specimens, scientists evaluated their specific gene expression profile to see if these tumors could be classified in to separate clusters. They were able to identify four different subtypes: differentiated, immunoreactive, mesenchymal, and proliferative groups. However, these subtypes could not be distinguished by their clinical outcome (ie, no poor or good prognostic groups could be distinguished). It may be explained by the significant heterogeneity that governs these cancers, and if so, highlights the importance of individualization of treatment.

The issue that stands in the way of tailored treatment is this: we have no data that proves a benefit to individualized therapy over standard of care. While true that cancer therapeutics has identified several therapies that target specific proteins (trastuzumab for HER-2 positive breast cancers, Imatinib for chronic myelogenous leukemia, cetuximab for K-ras wild-type colorectal cancer) a more widespread individualization of treatment that improves survival remains illusive and the design of such studies continues to be a challenge.

So, where does this leave us today? We are fortunate that the possibilities available to patients with cancer continues to expand, with both traditional chemotherapy agents (eribulin in breast cancer) and biologic therapies (sorafenib in hepatocellular cancer) being approved. Patients and their physicians must continue to demand a high level of proof before wide acceptance of any platform that claims to predict drug sensitivity, drug resistance, or the drugs "most likely to work". Until such a time that any technology can prove that survival is positively impacted by individualization, one risks more harm than benefit from denying standard agents to anyone in whom that treament would be otherwise be used.

For more information: National Institutes of Health