A Review on Curcumin and its Derivatives as Inhibitors of EGFR Signaling in Cancer

Abstract

Epidermal Growth Factor Receptor (EGFR) is a central regulator of cellular proliferation, survival, migration, and differentiation, and its dysregulation is implicated in the pathogenesis of multiple human malignancies. While EGFR-targeted therapies such as tyrosine kinase inhibitors and monoclonal antibodies have shown clinical benefit, their use is limited by intrinsic and acquired resistance, toxicity, and tumor heterogeneity. Curcumin, a class of polyphenolic compounds derived from Curcuma longa, has gained considerable attention for its anticancer properties and ability to modulate multiple oncogenic signaling pathways. This review provides a comprehensive and critical analysis of curcumin as an inhibitor of EGFR signaling. There is much evidence from in vitro and in vivo models across EGFR-driven cancers, particularly triple-negative breast cancer, non-small cell lung cancer, and colorectal cancer, that curcumin acts as a natural EGFR inhibitor. Additionally, curcumin may influence downstream signaling pathways, including PI3K/AKT and MAPK, thereby contributing to the suppression of tumor growth and progression. However, its poor bioavailability, limited solubility, and variable therapeutic responses remain significant challenges. Further mechanistic studies and well-designed clinical trials are needed to establish its therapeutic potential and clinical relevance.