The promise of precision medicine for cancer is already being realized with the recent introduction of many targeted therapies, some with companion diagnostic tests that identify patients most likely to benefit from treatment. The utility of molecular profiling of cancer to identify actionable aberrations has been suggested by several small clinical trials conducted in patients with advanced cancer and by many anecdotes but is yet to be proven in well-designed, prospective, randomized trials. Several trials that will definitively test this strategy are now underway or soon to be launched. Melanoma, a disease once largely untreatable when metastatic, may be a paradigm for understanding how the molecular drivers of a disease can lead to highly effective targeted therapies, as well as for realizing the enormous therapeutic potential of unleashing the immune system against cancer to produce long-term disease control. Looking to the future, advanced omics technologies and computational techniques will enable assessment of not only genomic variants, as performed today, but also of pathway and network aberrations that will greatly facilitate selection of drug combinations likely to benefit specific patients. As our deepening understanding of tumor biology converges with rapid advances in measurement science and technology and computational analysis, we have an enormous opportunity to create a future for precision medicine in oncology that provides for highly specific, minimally toxic, and dramatically effective treatment for each patient.
The future of EPAC-targeted therapies: agonism versus antagonism