Abstract:
HER3 (Human Epidermal Growth Factor Receptor 3) is frequently overexpressed in various cancers, including non-small cell lung cancer (NSCLC), with a prevalence of 83% in primary tumors. Its involvement in tumorigenesis and resistance to targeted therapies makes HER3 a promising target for cancer treatment. Despite being initially considered \"undruggable\" due to its lack of catalytic activity, significant progress has been made in the development of anti-HER3 therapeutics. Monoclonal antibodies such as lumretuzumab, seribantumab, and patritumab have shown potential in targeting HER3 to overcome resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). Additionally, antibody-drug conjugates (ADCs) like HER3-DXd (patritumab deruxtecan) are new drug candidates that have demonstrated selective delivery of cytotoxic chemicals to NSCLC cells by exploiting HER3\'s widespread expression, minimizing cytotoxicity. This review aims to evaluate the efficacy of current HER3 therapeutics in development and their therapeutic potential in NSCLC, incorporating evidence from clinical trials.
摘要:
HER3(人表皮生长因子受体3)在各种癌症中经常过表达,包括非小细胞肺癌(NSCLC),原发性肿瘤的患病率为83%。它参与肿瘤发生和对靶向治疗的抗性使HER3成为癌症治疗的有希望的靶标。尽管由于缺乏催化活性而最初被认为“不可用”,抗HER3疗法的开发取得了重大进展。单克隆抗体如lumretuzumab,seribantumab,和帕特单抗已经显示出靶向HER3克服表皮生长因子受体(EGFR)酪氨酸激酶抑制剂(TKIs)耐药性的潜力。此外,抗体-药物偶联物(ADC)如HER3-DXd(patritumabderuxtecan)是新的候选药物,已证明通过利用HER3的广泛表达将细胞毒性化学物质选择性递送至NSCLC细胞,最小化细胞毒性。这篇综述旨在评估当前HER3治疗的疗效及其在非小细胞肺癌中的治疗潜力。纳入临床试验的证据。