Biomarker-driven studies in metastatic colorectal cancer (mCRC): Challenges and opportunities

The search for molecular biomarkers that predict the likely response to targeted treatments for metastatic colorectal cancer (mCRC) has yielded many promising candidates, yet only the (K)RAS mutation has so far been incorporated into clinical practice. Other promising biomarkers of response to anti-angiogenic agents and the multikinase inhibitor, regorafenib, are currently under investigation in ongoing studies. While a growing understanding of cancer signaling pathways in mCRC presents multiple opportunities for the development of tumor-targeted therapies, inter- and intra-tumor heterogeneity and the dynamic process of tumor evolution during treatment present major challenges to biomarker research and drug development. Overcoming these challenges requires the application of novel approaches to the assessment of biomarkers and innovative clinical trials that employ statistical approaches that maximize efficiency and minimize exposure to underperforming treatments. Ongoing, contemporary biomarker-driven studies in mCRC have already yielded salient lessons that will inform the design of future studies. These will also benefit from the combined expertise of major research consortia using systems biology approaches to the identification and validation of predictive biomarkers in mCRC. With such a powerful global commitment to biomarker research in mCRC, there seems little doubt that before too long, new predictive biomarkers will be available to help guide clinical decision-making in mCRC, ensuring the right treatment is selected for the right patient at the right time.