Division of Endocrinology, Central Drug Research Institute, CSIR, Lucknow-226001, Uttar Pradesh, India.
Med Res Rev. 2012 Jan;32(1):166-215. doi: 10.1002/med.20209. Epub 2010 Oct 25.
Breast cancer is the most common cancer diagnosed in women and the second most common cause of female cancer-related deaths, with more than one million new cases diagnosed per year throughout the world. With the recent advances in the knowledge of cellular processes and signaling pathways involved in the pathogenesis of breast cancer, the current focus of researchers and clinicians is to develop novel treatment strategies that can be included in the armamentarium against breast cancer. With the failure of endocrine-targeted therapy and the development of resistance to existing chemotherapy, the most explored pathway as next generation target for breast cancer therapy has been the epidermal growth factor receptor (EGFR) (ErbB-1)/herceptin-2 (HER-2) (ErbB-2) pathway. This review focuses on the rationale for targeting members of ErbB receptor family and numerous agents that are in use for inhibiting the pathway. The mechanism of action, preclinical and clinical trial data of the agents that are in use for targeting the EGFR/HER-2 pathway and the current status, thereof, have been discussed in detail. In addition, the future clinical trial promises these agents hold either as monotherapy or as combination therapy with conventional agents or with other antisignaling agents have been pondered, so as to provide better and more efficacious treatment strategies for breast cancer patients.
乳腺癌是女性最常见的癌症,也是女性癌症相关死亡的第二大常见原因,全球每年诊断出超过 100 万例新病例。随着对参与乳腺癌发病机制的细胞过程和信号通路的知识的最新进展,研究人员和临床医生目前的重点是开发新的治疗策略,可以将其纳入乳腺癌的治疗方案中。由于内分泌靶向治疗的失败和现有化疗药物耐药性的发展,表皮生长因子受体 (EGFR) (ErbB-1)/曲妥珠单抗 (HER-2) (ErbB-2) 途径已成为乳腺癌治疗的下一代靶标中最受关注的途径。本文重点介绍了针对 ErbB 受体家族成员和许多用于抑制该途径的药物的基本原理。详细讨论了用于靶向 EGFR/HER-2 途径的药物的作用机制、临床前和临床试验数据及其现状。此外,还考虑了这些药物作为单一疗法或与常规药物或其他抗信号药物联合治疗的未来临床试验前景,以便为乳腺癌患者提供更好、更有效的治疗策略。