Experimental Therapeutics Unit, Medical Oncology Department, Hospital Clínico San Carlos and IdISSC, Madrid, Spain.
Centro de Investigación Biomédica en Red Cáncer (CIBERONC), Madrid, Spain.
Breast Cancer Res. 2020 Jan 31;22(1):15. doi: 10.1186/s13058-020-1252-7.
There has been substantial interest in HER2 intratumoral heterogeneity as an explanation for the development of resistance to anti-HER2 therapies in breast cancer, particularly to trastuzumab emtansine (T-DM1).
Through a literature-based approach, we discuss mechanisms of resistance to HER2-targeting antibody-drug conjugates (ADCs) in breast cancer.
We describe results from clinical studies reporting the effect of anti-HER2 strategies particularly ADCs and their mechanistic effect. We review biological findings underlying HER2 heterogeneity and its implication in the development of novel anti-HER2 drugs including new ADCs in clinical development like trastuzumab deruxtecan (DS-8201).
We suggest potential mechanisms to optimize these compounds and their future clinical implementation.
人们对 HER2 肿瘤内异质性产生了浓厚的兴趣，认为这是乳腺癌对抗 HER2 治疗（尤其是曲妥珠单抗-美坦新偶联物[T-DM1]）产生耐药性的原因。
通过文献回顾的方法，我们讨论了乳腺癌中针对 HER2 靶向抗体药物偶联物（ADC）产生耐药的机制。
我们描述了临床研究中报告的抗 HER2 策略（尤其是 ADC）及其作用机制的结果。我们回顾了 HER2 异质性的生物学基础及其对新型抗 HER2 药物（包括临床开发中的新型 ADC，如曲妥珠单抗 deruxtecan [DS-8201]）发展的影响。
我们提出了优化这些化合物及其未来临床应用的潜在机制。
