CCR 20th Anniversary Commentary: RAS as a Biomarker for EGFR-Targeted Therapy for Colorectal Cancer-From Concept to Practice

摘要

Clinical data support the use of EGFR mAbs in patients with metastatic colorectal cancer (mCRC) with wild-type RAS status. This notion, hypothesized in the review article by Camp, Ellis, and colleagues in the January 1,2005, issue of Clinical Cancer Research, serves as an example of the successful application of basic science principles to clinical practice. The exclusion of patients with mCRC with Ras-mutated tumors from therapy with EGFR mAbs has led to improved outcomes while sparing patients unnecessary and potentially harmful therapy. The therapeutic potential of mAbs targeting the EGFR was established by promising preclinical studies and subsequent early-phase clinical trials in patients with metastatic colorectal cancer (mCRC; ref. 1). Ultimately, in 2004, the FDA approved the human-mouse chimeric EGFR mAb, cetuximab, for use in chemotherapy-refractory patients with mCRC. Similarly, panitumu-mab, a fully human EGFR mAb, was FDA approved for similar indications in 2006, and ultimately both drugs were subsequently approved in the first-line setting in combination with chemotherapy. However, the earliest clinical trials investigating EGFR mAbs in mCRC demonstrated that these agents only provided modest benefit when used in combination with chemotherapy. Around this time, a concerted effort to identify predictive markers for EGFR-targeted therapies was undertaken simultaneous to advances in genomic sequencing. As principal investigator of a laboratory, the senior author of this article (L.M. Ellis) learned early on in his career that the best way to educate a trainee on a topic was to have this individual write a review article. This strategy exposes trainees to the entire field of the topic of interest, requiring a critical evaluation of the literature, and identifying knowledge gaps.