EGFR, HER2, ER, and AR Signaling in Cancer: Dysregulation, Therapeutic Resistance, and Targeted Therapies

Receptor dysregulation is a hallmark of cancer and a major driver of tumor initiation, progression, and therapeutic resistance. Among the most clinically relevant receptors are the epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), estrogen receptor (ER), and androgen receptor (AR), which regulate critical processes including cell proliferation, survival, and metastasis. Genetic alterations, receptor overexpression, and aberrant signaling can lead to persistent activation of these pathways, promoting oncogenic progression. Advances in the understanding of EGFR, HER2, ER, and AR signaling have enabled the development of targeted therapies that have significantly improved clinical outcomes. However, therapeutic resistance, signaling crosstalk, and tumor heterogeneity continue to limit treatment efficacy. This review summarizes the mechanisms underlying the dysregulation of these receptor pathways, their roles in cancer development, and current and emerging therapeutic strategies targeting receptor-driven malignancies. A better understanding of these signaling networks may facilitate the development of more effective biomarkers and precision oncology approaches.