Abstract
The targeting of EGF receptors (EGFRs) in metastatic colorectal cancer has improved the outcome of patients with KRAS wild-type tumors. However, these improvements have been modest and do not translate across all patients with KRAS wild-type tumors. Better understanding of the EGFR pathway has led to the exploration of variable novel potential biomarkers of resistance and response to anti-EGFR therapy. This manuscript will focus on recently identified mechanisms of resistance to anti-EGFR therapy in KRAS wild-type colorectal cancer. Subsequently, an assessment will be presented on how the current understanding of some of these mechanisms of resistance has led, and will lead, to novel therapeutic opportunities in the management of colorectal cancer.
MeSH terms
-
Antibodies, Monoclonal / pharmacology
-
Antibodies, Monoclonal / therapeutic use
-
Class I Phosphatidylinositol 3-Kinases
-
Colorectal Neoplasms / drug therapy*
-
Colorectal Neoplasms / genetics*
-
Colorectal Neoplasms / pathology
-
Drug Resistance, Neoplasm / drug effects*
-
Drug Resistance, Neoplasm / genetics
-
ErbB Receptors / genetics*
-
ErbB Receptors / immunology
-
GTP Phosphohydrolases / genetics
-
Gene Expression Regulation, Neoplastic
-
Genes, ras*
-
Humans
-
Membrane Proteins / genetics
-
Molecular Targeted Therapy / methods*
-
Mutation
-
PTEN Phosphohydrolase / genetics
-
Phosphatidylinositol 3-Kinases / genetics
-
Precision Medicine / methods
-
Proto-Oncogene Proteins B-raf / genetics
-
Proto-Oncogene Proteins c-met / genetics
-
Receptor, ErbB-2 / genetics
-
Receptor, ErbB-3 / genetics
Substances
-
Antibodies, Monoclonal
-
Membrane Proteins
-
Phosphatidylinositol 3-Kinases
-
Class I Phosphatidylinositol 3-Kinases
-
PIK3CA protein, human
-
ERBB2 protein, human
-
ERBB3 protein, human
-
ErbB Receptors
-
MET protein, human
-
Proto-Oncogene Proteins c-met
-
Receptor, ErbB-2
-
Receptor, ErbB-3
-
BRAF protein, human
-
Proto-Oncogene Proteins B-raf
-
PTEN Phosphohydrolase
-
PTEN protein, human
-
GTP Phosphohydrolases
-
NRAS protein, human