Language
English
Publication Date
12-1-2024
Journal
Onco
DOI
10.3390/onco4040019
PMID
40727266
PMCID
PMC12302966
PubMedCentral® Posted Date
7-28-2025
PubMedCentral® Full Text Version
Author MSS
Abstract
The epidermal growth factor receptor (EGFR) plays a critical role in regulating essential cellular processes that are frequently hijacked to promote cancer. In colorectal cancer (CRC) in particular, the EGFR signaling pathway is frequently hyperactivated via receptor and/or ligand overexpression and downstream oncogenic mutations. Current EGFR-targeted therapies for metastatic CRC (mCRC) include the monoclonal antibodies (mAbs) cetuximab and panitumumab. However, intrinsic and acquired resistance to EGFR-targeted mAbs are commonly observed. Thus, additional biomarkers are necessary to better understand patient sensitivity to EGFR-targeted therapies. Furthermore, therapeutic targeting of alternative EGFR pathway components may serve as one mechanism to overcome EGFR-targeted mAb resistance. In this review, we discuss the mounting evidence supporting EGFR ligands epiregulin (EREG) and amphiregulin (AREG), which are overexpressed in CRC with potential key roles in tumor progression, as predictive biomarkers for EGFR-targeted therapy sensitivity as well as mediators of therapy resistance; though further studies are necessary to validate the prognostic roles and mechanisms by which these ligands contribute to resistance. Additionally, we review recent advances towards therapeutic targeting of EREG and AREG in cancer through the development and use of EREG- and AREG-targeted monoclonal antibodies (mAbs) as well as antibody-drug conjugates (ADCs). We conclude with a discussion on the roadblocks to clinical implementation of EREG and AREG as biomarkers as well as approaches to enhance efficacy of current EREG- and AREG-targeted strategies.
Keywords
epiregulin, amphiregulin, epidermal growth factor receptor, colorectal cancer, cetuximab, panitumumab, biomarkers, monoclonal antibodies, antibody-drug conjugates
Published Open-Access
yes
Recommended Citation
Cara Guernsey-Biddle, Peyton High, and Kendra S Carmon, "Exploring the Potential of Epiregulin and Amphiregulin as Prognostic, Predictive, and Therapeutic Targets in Colorectal Cancer" (2024). The Brown Foundation: Institute of Molecular Medicine. 15.
https://digitalcommons.library.tmc.edu/molecular_med/15