文章：

RET基因变异癌症——生物学、诊断与靶向治疗活性的肿瘤不可知论综述

RET-Altered Cancers—A Tumor-Agnostic Review of Biology, Diagnosis and Targeted Therapy Activity

原文发布日期：17 August 2023

DOI: 10.3390/cancers15164146

类型: Article

开放获取: 是

英文摘要：

RETalterations, such as fusions or mutations, drive the growth of multiple tumor types. These alterations are found in canonical (lung and thyroid) and non-canonical (e.g., gastrointestinal, breast, gynecological, genitourinary, histiocytic) cancers.RETalterations are best identified via comprehensive next-generation sequencing, preferably with DNA and RNA interrogation for fusions. Targeted therapies forRET-dependent cancers have evolved from older multikinase inhibitors to selective inhibitors of RET such as selpercatinib and pralsetinib. Prospective basket trials and retrospective reports have demonstrated the activity of these drugs in a wide variety ofRET-altered cancers, notably those withRETfusions. This paved the way for the first tumor-agnostic selective RET inhibitor US FDA approval in 2022. Acquired resistance to RET kinase inhibitors can take the form of acquired resistance mutations (e.g., RET G810X) or bypass alterations.

摘要翻译： 

RET基因的融合或突变等改变驱动多种类型肿瘤的生长。这些改变可见于典型（肺和甲状腺）及非典型（如胃肠道、乳腺、妇科、泌尿生殖系统、组织细胞性）癌症。通过综合性新一代测序技术，特别是结合DNA与RNA检测融合突变，能够最有效地识别RET基因改变。针对RET依赖性癌症的靶向治疗已从早期的多激酶抑制剂发展为选择性RET抑制剂，如塞普替尼和普拉替尼。前瞻性篮式试验和回顾性研究报告证实了这些药物在多种RET基因改变癌症中的疗效，尤其对携带RET融合突变的肿瘤效果显著。这为2022年美国FDA首次批准不区分肿瘤类型的RET选择性抑制剂奠定了基础。RET激酶抑制剂的获得性耐药可能表现为获得性耐药突变（如RET G810X）或旁路途径改变。

原文链接：

RET-Altered Cancers—A Tumor-Agnostic Review of Biology, Diagnosis and Targeted Therapy Activity