Epidermal growth factor receptor antagonists in colorectal cancer: emerging strategies for precision therapy.

Introduction: The global prevalence of colorectal cancer highlights the need to enhance treatment strategies for improved patient outcomes. The pivotal role of epidermal growth factor receptor (EGFR) signaling in regulating cellular processes for this disease pinpoints its value as a therapeutic target, despite the emergence of resistance mechanisms over time.

Areas Covered: This review discusses the clinical evidence supporting the use of EGFR inhibitors in molecularly-selected patients based on molecular characteristics (notably V600E and G12C) including combination approaches targeting different points in in the signaling pathway, as well as strategies such as EGFR inhibitor rechallenge.

Targeting G12C Mutation in Colorectal Cancer, A Review: New Arrows in the Quiver.

Kirsten rat sarcoma virus oncogene homolog () is the most frequently mutated oncogene in human cancer. In colorectal cancer (CRC), mutations are present in more than 50% of cases, and the glycine-to-cysteine mutation at codon 12 ( G12C) occurs in up to 4% of patients. This mutation is associated with short responses to standard chemotherapy and worse overall survival compared to non-G12C mutations.

The predictive role of ERBB2 point mutations in metastatic colorectal cancer: A systematic review.

ERBB2 amplification is a driver oncogenic alteration in many cancers and it has recently been incorporated among therapeutically actionable biomarkers also in metastatic colorectal cancer (mCRC). In contrast, the role of ERBB2 point mutations, which are detectable in up to 3% of CRC patients, remains to be assessed. In this systematic review, we collected preclinical and clinical data addressing the role of ERBB2 point mutations in mCRC patients as a predictive biomarker for anti-EGFR and anti-HER2 targeted agents, and as mechanism of acquired resistance to ERBB2 amplified mCRC treated with any anti-HER2 regimen.

Liquid Biopsy for Prognosis and Treatment in Metastatic Colorectal Cancer: Circulating Tumor Cells vs Circulating Tumor DNA.

Liquid biopsy recently gained widespread attention as a noninvasive alternative/complementary technique to tissue biopsy in patients with cancer. As technological advances have improved both feasibility and turnaround time, liquid biopsy has expanded tumor molecular analysis with acknowledgement of both spatial and temporal heterogeneity, overcoming many limitations of traditional tissue biopsy. Because of its diagnostic, prognostic, and predictive value, liquid biopsy has been extensively studied also in metastatic colorectal cancer.

HER2 Positivity Predicts Unresponsiveness to EGFR-Targeted Treatment in Metastatic Colorectal Cancer.

Background: HER2 amplification is detected in 3% of patients with colorectal cancer (CRC), making tumors in the metastatic setting vulnerable to double pharmacological HER2 blockade. Preclinical findings show that it also might impair response to anti-epidermal growth factor receptor (EGFR) treatment.

Subjects And Methods: Patients with exon 2 wild-type metastatic CRC underwent molecular screening of HER2 positivity by HERACLES criteria (immunohistochemistry 3+ or 2+ in ≥50% of cells, confirmed by fluorescence in situ hybridization).