Advances in HER2-Targeted Tumor Therapy: Molecular Mechanisms, Treatment Strategies and Clinical Challenges

Abstract

Human epidermal growth factor receptor 2 (HER2) is a vital oncotherapeutic target across multiple solid tumors, covering breast, gastric/gastroesophageal junction, non-small cell lung, colorectal, biliary, urothelial, cervical, endometrial, salivary gland, and ovarian cancers, as well as esophageal adenocarcinoma. Clarifying HER2-mediated oncogenic signaling and identifying validated treatment strategies are critical for standardized clinical practice and innovative drug discovery. This review begins with HER2 structural features and downstream oncogenic signaling, then summarizes therapeutic frameworks for HER2-positive cancers, including conventional regimens, single targeted agents, and combination therapies. Three major clinical obstacles—drug resistance, treatment-related toxicities and tumor heterogeneity—are analyzed alongside corresponding solutions, followed by prospects in novel drug development, precision medicine and multidisciplinary cooperation. Current clinical data show that single-agent therapies possess modest antitumor activity; chemo-targeted combinations partially enhance efficacy yet are hindered by resistance and heterogeneity. Further innovations in precision medicine are urgently needed to enable personalized management. This work systematically reviews pan-cancer HER2-related oncogenic mechanisms and the full spectrum of targeted regimens offering mechanistic and clinical references for precision therapy and new drug research of HER2-positive solid tumors.