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Published on: October 27, 2014
Bevacizumab-based treatment in colorectal cancer with a NRAS Q61K mutation
Filip Janku1, Jennifer J Wheler2, David S Hong2
1Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program), The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Box 0455, Houston, TX, 77030, USA. fjanku@mdanderson.org.
Abstract:
Despite development of new therapies, metastatic colorectal cancer (mCRC) largely remains an incurable disease. Approximately 2-6% of colorectal cancers harbor NRAS mutations. The anti-VEGF antibody bevacizumab is a backbone of most therapeutic regimens; however, biomarkers predicting its activity are not known. We report two cases of mCRC with a Q61K NRAS mutation that had a favorable response to bevacizumab and the histone deacetylase inhibitor valproic acid. In contrast, none of ten patients with wild-type NRAS or unknown NRAS status and mutated KRAS (NRAS and KRAS mutations are mutually exclusive) responded to the same regimen. These results suggest that NRAS mutation merits further investigation as a potential biomarker predicting the efficacy of bevacizumab-based treatment.
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