EGFR Signaling and Related Pathways: Potential Targets for CRISPR‐Mediated Gene Editing System in the Colorectal Cancer

As the original member of the huge family of growth factor receptors, the epidermal growth factor receptor (EGFR) has shown inherent tyrosine kinase activity. In addition to its prototypic ligand, EGF, it is activated by TGF‐α. EGFR and its ligand contribute to the pathogenesis of colorectal cancer and resistance to targeted therapy. The novel genome editing system, CRISPR/Cas9 has facilitated precise editing of oncogenic loci. This technique has been used in the context of colorectal cancer to either down‐regulate EGFR signaling or amend/induce certain mutations affecting the response to tyrosine kinase inhibitors. This review summarizes the application of the mentioned technique in modulation of EGFR signaling and related pathways in the colorectal cancer. Moreover, we uniquely focused on compiling and interpreting results from CRISPR/Cas9 loss‐of‐function screens that directly investigate resistance to EGFR inhibition in colorectal cancer models. We also analyzed how these screens have identified key genes and pathways—within and beyond the canonical EGFR cascade—that drive resistance, providing a novel, gene‐centric perspective on this critical clinical problem.