Abstract
Targeting the epidermal growth factor receptor (EGFR) either alone or in combination with chemotherapy is effective for patients with RAS wild type metastatic colorectal cancer (mCRC). However, only a small percentage of mCRC patients are sensitive to anti-EGFR therapy and even the best cases finally become refractory to this therapy. It has become apparent that the RAS mutations correlate with resistance to anti-EGFR therapy. However, these resistance mechanisms only account for nearly 35% to 50% of nonresponsive patients, suggesting that there might be additional mechanisms. In fact, several novel pathways leading to escape from anti-EGFR therapy have been reported in recent years. In this review, we provide an overview of known and novel mechanisms that contribute to both primary and acquired anti-EGFR therapy resistance, and enlist possible treatment strategies to overcome or reverse this resistance.
Highlights
Colorectal cancer (CRC) ranks among the third most common human malignant diseases and is one of the leading causes of cancer-related deaths globally [1, 2]
Two representative examples of such drugs are cetuximab and panitumumab, two monoclonal antibodies against the epidermal growth factor receptor (EGFR), which have been proven to be effective for patients with RAS wild type (RASWT) metastatic colorectal cancer (mCRC) in randomized clinical trials [3,4,5,6,7,8,9]
KRAS exon 2 mutations were significantly associated with non-response and shorter progression-free survival (PFS) and overall survival (OS) in mCRC patients treated with cetuximab or panitumumab
Summary
Colorectal cancer (CRC) ranks among the third most common human malignant diseases and is one of the leading causes of cancer-related deaths globally [1, 2]. These data suggest that the BRAF V600E mutation contributes to resistance to anti-EGFR moAbs in patients with chemotherapy-refractory KRAS wild-type mCRC. KRAS exon 2 (codon 12 and 13) mutations were significantly associated with non-response and shorter PFS and OS in mCRC patients treated with cetuximab or panitumumab (with or without chemotherapy).
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