Recent Advances in Targeting the EGFR Signaling Pathway for the Treatment of Metastatic Colorectal Cancer

• Published in: International journal of molecular sciences Vol. 18; no. 4; p. 752
• Main Authors: Miyamoto, Yuji, Suyama, Koichi, Baba, Hideo
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 02.04.2017; MDPI
• Subjects: Antibodies, Monoclonal - therapeutic use; Colorectal cancer; Colorectal Neoplasms - drug therapy; Colorectal Neoplasms - genetics; Colorectal Neoplasms - metabolism; Drug Resistance, Neoplasm - genetics; Humans; Metastasis; Molecular Targeted Therapy - methods; Molecular Targeted Therapy - trends; Mutation; Neoplasm Metastasis; Proto-Oncogene Proteins p21(ras) - antagonists & inhibitors; Proto-Oncogene Proteins p21(ras) - genetics; Proto-Oncogene Proteins p21(ras) - metabolism; Receptor, Epidermal Growth Factor - antagonists & inhibitors; Receptor, Epidermal Growth Factor - genetics; Receptor, Epidermal Growth Factor - metabolism; Review; Signal Transduction - drug effects; Signal Transduction - genetics; metastatic colorectal cancer; secondary resistance; chemotherapy; epidermal growth-factor receptor signaling (EGFR)
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms18040752

Outcomes for metastatic colorectal cancer (mCRC) patients have been improved by treatment with anti-epidermal growth factor receptor (anti-EGFR) antibodies, particularly when combined with predictive biomarkers to select patients lacking RAS mutations. New technologies such as liquid biopsy and next-generation sequencing have revealed that potential mechanisms of resistance to anti-EGFR therapies act through acquired mutations of KRAS and the EGFR ectodomain. Mutations in cross-talking molecular effectors that participate in downstream EGFR signaling are also negative predictors for anti-EGFR therapy. In the current review, we describe recent advances in anti-EGFR therapy and discuss new treatment strategies to target downstream RAS-MAPK signaling in mCRC.