KRAS p.G13D mutations are associated with sensitivity to anti-EGFR antibody treatment in colorectal cancer cell lines

Abstract

Since KRAS p.G13D-mutated tumour cells may respond to EGFR-targeted therapy, we suggest including subtype analysis of KRAS mutations in prospective clinical trials. In KRAS wild-type tumour cells, BRAF mutations and loss of EGFR or PTEN expression may lead to resistance to EGFR-targeted therapy and should be considered as additional negative predictive biomarkers.

KRAS exon 2 mutations influence activity of regorafenib in an SW48-based disease model of colorectal cancer

“…In mCRC, as described by various authors, mutations located in codon 13 (G13D) might be associated with some response to cetuximab in pretreated patients and in patients following cetuximab-based first-line regimens. These data are supported by in vitro models of colorectal cancer [13][14]16].…”

PRMT1-mediated methylation of the EGF receptor regulates signaling and cetuximab response

“…Therefore, American Society of Clinical Oncology recommended cetuximab treatment for only patients with WT KRAS (21). However, there is increasing evidence showing that WT KRAS is not sufficient to confer sensitivity to cetuximab (22)(23)(24), and some patients with mutant KRAS are still sensitive to cetuximab (16,(25)(26)(27)(28). These findings suggest that further investigation into the underlying mechanisms of cetuximab resistance and identification of a better predictor for cetuximab response are ing of chemotherapeutic agents have improved the response and survival rate of colorectal patients.…”

KRAS status and resistance to epidermal growth factor receptor tyrosine‐kinase inhibitor treatment in patients with metastatic colorectal cancer: a meta‐analysis

“…In mCRC, the most frequently detected alterations in EGFR signalling pathways are KRAS mutations. KRAS mutations occur in approximately 30-50% of patients with mCRC [7]. Recent data suggest that KRAS mutations are negative predictors of benefit from treatment by EGFR TKIs in patients with disseminated disease [8], but these results are inconclusive.…”

“…KRAS mutations have been identified in approximately 30-50% of patients with CRC [7]. In addition, several studies have indicated that the presence of mutant KRAS in lung and CRC tumours correlates with poor prognosis and is associated with a lack of response to EGFR inhibitors [8].…”