Stratification of colorectal cancer patients based on various sequencing platforms and tumor mutational burden

Colorectal cancer (CRC) is the third most common type of cancer in the United States. Although chemotherapy, radiation and targeted therapies can improve survival rates, recent studies have shown the potential benefit of immunotherapies to improve outcomes for patients with advanced CRC. Targeted therapies that use monoclonal antibodies (mAbs) to EGFR have been shown to benefit some CRC patients. Until recently, KRAS has been the only predictive biomarker for anti-EGFR therapy for metastatic CRC. However, 40% to 60% of patients with wild-type KRAS do not respond to anti-EGFR therapy. Therefore, to accurately predict patients9 response to treatments and improve clinical outcomes, additional prediction and treatment methods are imperative. One of the many efforts to improve prediction for CRC patient9s response to the anti-EGFR therapy is the development of gene expression based RAS signature scores for identification of RAS activated tumors independent of mutations in the KRAS gene. There is also considerable effort being placed on combinations of targeted therapy and immunotherapies to improve responses for these cancers. Previously, we have stratified 55 CRC samples by applying a RAS gene signature score which measures MEK pathway functional output independent of tumor genotype. We showed that samples that have RAS activating mutations such as KRAS and BRAF have significant higher RAS scores (p Citation Format: Fang Yin Lo, Claire Olson, Kerry Deutsch, Tuuli Saloranta, Inah Golez, Timothy Yeatman, Steven Anderson, Anup Madan. Stratification of colorectal cancer patients based on various sequencing platforms and tumor mutational burden [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5379.