Oncogenic fingerprint of epidermal growth factor receptor pathway and emerging epidermal growth factor receptor blockade resistance in colorectal cancer

Zain A. Sobani, Ashwin Sawant, Mikram Jafri, Amit Keith Correa, Ibrahim Halil Sahin

Research output: Contribution to journalReview articlepeer-review

6 Scopus citations

Abstract

Epidermal growth factor receptor (EGFR) has been an attractive target for treatment of epithelial cancers, including colorectal cancer (CRC). Evidence from clinical trials indicates that cetuximab and panitumumab (anti- EGFR monoclonal antibodies) have clinical activity in patients with metastatic CRC. The discovery of intrinsic EGFR blockade resistance in Kirsten RAS (KRAS)-mutant patients led to the restriction of anti-EGFR antibodies to KRAS wild-type patients by Food and Drug Administration and European Medicine Agency. Studies have since focused on the evaluation of biomarkers to identify appropriate patient populations that may benefit from EGFR blockade. Accumulating evidence suggests that patients with mutations in EGFR downstream signaling pathways including KRAS, BRAF, PIK3CA and PTEN could be intrinsically resistant to EGFR blockade. Recent whole genome studies also suggest that dynamic alterations in signaling pathways downstream of EGFR leads to distinct oncogenic signatures and subclones which might have some impact on emerging resistance in KRAS wild-type patients. While anti-EGFR monoclonal antibodies have a clear potential in the management of a subset of patients with metastatic CRC, further studies are warranted to uncover exact mechanisms related to acquired resistance to EGFR blockade.

Original languageEnglish
Pages (from-to)340-351
Number of pages12
JournalWorld Journal of Clinical Oncology
Volume7
Issue number5
DOIs
StatePublished - 10 Oct 2016
Externally publishedYes

Keywords

  • BRAF
  • Cetuximab
  • Epidermal growth factor receptor
  • Epidermal growth factor receptor blockade resistance
  • Kirsten RAS
  • Oncogenic signature
  • Panitumumab

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