HER2 异质性与抗 HER2 抗体药物偶联物耐药性。
HER2 heterogeneity and resistance to anti-HER2 antibody-drug conjugates.
机构信息
Experimental Therapeutics Unit, Medical Oncology Department, Hospital Clínico San Carlos and IdISSC, Madrid, Spain.
Centro de Investigación Biomédica en Red Cáncer (CIBERONC), Madrid, Spain.
出版信息
Breast Cancer Res. 2020 Jan 31;22(1):15. doi: 10.1186/s13058-020-1252-7.
Abstract
BACKGROUND
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).
METHODS
Through a literature-based approach, we discuss mechanisms of resistance to HER2-targeting antibody-drug conjugates (ADCs) in breast cancer.
RESULTS
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).
CONCLUSIONS
We suggest potential mechanisms to optimize these compounds and their future clinical implementation.
摘要
背景
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。
方法
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。
结果
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。
结论
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。
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