The personalization of cancer care is rooted in the premise that there are subsets of patients with tumors harboring clinically relevant targets for patient-specific treatments. CRC is historically a disease that has been notable for its dearth of biomarkers that are predictive of response to targeted therapies. In a rapidly evolving era of personalized oncology, CRC has been eclipsed by other tumor types, with very little of the abundant genomic data bearing any relevance for clinical decision-making. BRAFV600E-mutated CRC is an exception, however, and considerable progress has been made in recent years to enhance both our understanding of the biology of BRAFV600E-mutant metastatic CRC and the associated therapeutic landscape.
While the overall prognosis for BRAFV600E mutant metastatic CRC is still far worse than for BRAF-wild-type CRC, the incremental progress thus far should be credited to the consistent incorporation of robust, high-quality correlative science into the clinical trials of BRAF inhibition and rapid translation of laboratory discovery into clinical trial design. Still, despite multiple studies showing evidence of response to combined BRAF/EGFR and BRAF/MEK inhibition, reported overall response rates and median PFS are modest at best, providing a sobering reminder of the ongoing need for therapeutic development for this disease. Looking ahead, we remain optimistic that ongoing efforts to impede signaling through the MAPK pathway through alternate targets will result in longer and more durable clinical responses for this unique subset of patients.
CU’s fellowship training in the Division of Hematology and Oncology at UCSF is supported by the Maisin Foundation and grant T32 AG000212 from the National Institute of Aging/Research Training in Geriatric Medicine. CEA is supported by the NIH and NCI under Award Number K08CA175143.
CEA is a consultant/advisory board member for Genentech/Roche and has received research funding from Novartis. The authors report no other conflicts of interest in this work.
Carling Ursem, Chloe E Atreya, Katherine Van Loon
Division of Hematology and Oncology, Department of Medicine, University of California, San Francisco, CA, USA
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Source: Gastrointestinal Cancer: Targets and Therapy.
Originally published March 22, 2018.