Roles of Her3 in carcinogenesis and advances in Her3-targeted cancer therapy

Abstract Among the epidermal growth factor receptor tyrosine kinases (EGFR) family, HER3 (Human epidermal growth factor receptor3) stands apart due to its minimal inherent intracellular kinase function. Its kinase domain contains specific amino acid variations not found in other family members, resulting in a stably inactive structural state. The inability to undergo homodimerization necessitates that HER3 pairs with a different receptor to become active; this heterodimerization triggers phosphorylation at its C-terminal tail. Elevated levels of HER3 are linked to enhanced tumor advancement and the spread of cancer, making it a prominent subject of study in oncology. Developing treatments focused on HER3 has become a significant strategy in cancer care. The upregulation of HER3 can initiate signaling through alternative routes that do not require EGFR, via association with other receptor types. This activates compensatory pathways and contributes to resistance against EGFR tyrosine kinase inhibitors (TKIs). Consequently, therapeutic strategies directed at HER3 may help address and surmount such resistance in cancer treatment, this review focuses on the progress in HER3-targeted therapeutic research for tumors and the latest breakthroughs in the development of drugs engaging HER3. Understanding the intricate mechanisms underlying HER3 function and its impact on cancer biology is crucial for devising more effective, precisely targeted interventions in the ongoing war against cancer.