Background:
Anti-EGFR monoclonal antibodies (mAbs) have become a relevant solution for the treatment of
patients with metastatic colorectal cancer. Current anti-EGFR monoclonal antibodies face a series of problems, including resistance and non-durable response, and RAS and BRAF mutations serve as exclusion criteria for treatment with anti-EGFR
mAbs. Advances in molecular tumor profiling and information on subsequent pathways responsible for disease progression
and drug resistance helped develop a new generation of anti-EGFR mAbs. These second-generation mAbs have been developed to overcome existing resistance mechanisms and to limit common side effects. For the moment, existing literature suggests that these novel anti-EGFR mAbs are far from finding their way to clinical practice soon.
Objective:
In this review, we summarize and evaluate current data regarding ongoing research and completed clinical trials
for different second-generation anti-EGFR monoclonal antibodies.
Conclusion:
Anti-EGFR mAbs exhibit efficacy in advanced colorectal cancer, but second-generation mAbs failed to prove
their benefit in the treatment of metastatic colorectal cancer. Understanding the biological basis of primary and acquired
drug resistance could allow scientists to design better clinical trials and develop improved second-generation mAbs.
Prospective patient stratification into robust cancer-cell intrinsic subtypes from colorectal cancer biopsies