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

被引：25

作者：

Desilets, Antoine ^{[1
]}

Repetto, Matteo ^{[1
,2
]}

Yang, Soo-Ryum ^{[1
]}

Sherman, Eric J. ^{[1
,3
]}

Drilon, Alexander ^{[1
,3
]}

机构：

[1] Mem Sloan Kettering Canc Ctr, New York, NY 10065 USA

[2] Univ Milan, Dept Oncol & Hemato Oncol, I-20133 Milan, Italy

[3] Weill Cornell Med Coll, Dept Med, New York, NY 10065 USA

来源：

CANCERS | 2023年 / 15卷 / 16期

关键词：

RET fusion; RET mutation; selpercatinib; pralsetinib; tumor agnostic; MULTIPLE ENDOCRINE NEOPLASIA; TYROSINE KINASE INHIBITOR; CELL LUNG-CANCER; THYROID PAPILLARY CARCINOMAS; POSITIVE SOLID TUMORS; OPEN-LABEL; GENE REARRANGEMENTS; ACQUIRED-RESISTANCE; CABOZANTINIB XL184; ANTITUMOR-ACTIVITY;

D O I：

10.3390/cancers15164146

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

RET alterations, 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. RET alterations are best identified via comprehensive next-generation sequencing, preferably with DNA and RNA interrogation for fusions. Targeted therapies for RET-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 of RET-altered cancers, notably those with RET fusions. 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.

引用

页数：24

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