Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Weil Cornell Medicine, New York, NY, USA.
Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Cancer Treat Rev. 2022 Sep;109:102436. doi: 10.1016/j.ctrv.2022.102436. Epub 2022 Jul 15.
Targeting the HER2 oncogene represents one of the greatest advances in the treatment of breast cancer. HER2 is one member of the ERBB-receptor family, which includes EGFR (HER1), HER3 and HER4. In the presence or absence of underling genomic aberrations such as mutations or amplification events, intricate interactions between these proteins on the cell membrane lead to downstream signaling that encourages cancer growth and proliferation. In this Review, we contextualize efforts to pharmacologically target the ErbB receptor family beyond HER2, with a focus on EGFR and HER3. Preclinical and clinical efforts are synthesized. We discuss successes and failures of this approach to date, summarize lessons learned, and propose a way forward that invokes new therapeutic modalities such as antibody drug conjugates (ADCs), combination strategies, and patient selection through rational biomarkers.
针对 HER2 癌基因是乳腺癌治疗的最大进展之一。HER2 是 ERBB 受体家族的一个成员，该家族还包括 EGFR（HER1）、HER3 和 HER4。在存在或不存在潜在的基因组异常（如突变或扩增事件）的情况下，细胞膜上这些蛋白质之间的复杂相互作用会导致下游信号传导，从而促进癌症的生长和增殖。在这篇综述中，我们将阐述在 HER2 之外，通过药理学靶向 ErbB 受体家族的努力，重点介绍 EGFR 和 HER3。综合了临床前和临床研究成果。我们讨论了迄今为止该方法的成败，总结了经验教训，并提出了一种新的治疗模式，如抗体药物偶联物（ADC）、联合策略和通过合理的生物标志物进行患者选择。
