PDF(Pubmed)
Abstract：
RET fusions occur in 1-2% of non-small cell lung cancer. Selpercatinib and pralsetinib are selective RET inhibitors with significant improvement of outcome in patients with tumor harboring RET fusion; however, resistance mechanisms appear frequently, mainly driven by MAPK pathway bypass, secondary RET mutations, or in 5% via MET amplification. Co-inhibition of RET and MET is a compelling strategy for overcoming MET-dependent resistance to RET inhibitors and potentially other inhibitors. To our knowledge, this is the first report of a novel ISOC1-RET fusion lung cancer with a durable complete response to selpercatinib, with resistance via MET amplification, which was overcome by the successful combination of selpercatinib and capmatinib.
摘要：
RET融合发生在1-2%的非小细胞肺癌中。Selpercatinib和pralsetinib是选择性RET抑制剂，可显著改善携带RET融合的肿瘤患者的预后；然而，耐药机制经常出现，主要由MAPK通路旁路驱动，继发性RET突变，或通过MET扩增在5%。RET和MET的共抑制是克服对RET抑制剂和潜在的其他抑制剂的MET依赖性抗性的令人信服的策略。据我们所知,这是首次报道新型ISOC1-RET融合肺癌，对selpercatinib具有持久的完全反应，通过MET扩增具有抗性，selpercatinib和卡马替尼的成功组合克服了这一难题.
