TRK inhibitor activity and resistance in TRK fusion-positive cancers in adults

被引：24

作者：

Harada, Guilherme ^{[1
,2
]}

Drilon, Alexander ^{[3
,4
]}

机构：

[1] Mem Sloan Kettering Canc Ctr, Dept Med, 1275 York Ave, New York, NY 10065 USA

[2] Sirio Libanes Hosp, Oncol Ctr, Rua Dona Adma Jafet 91, BR-01308050 Sao Paulo, Brazil

[3] Mem Sloan Kettering Canc Ctr, Dept Med, 885 2nd Ave, New York, NY 10017 USA

[4] Weill Cornell Med Coll, Dept Med, 1300 York Ave, New York, NY 10065 USA

来源：

CANCER GENETICS | 2022年 / 264卷

关键词：

NTRK gene fusions; TRK; TRK fusion cancer; TRK inhibitors; SOLID TUMORS; RECEPTOR GENE; NTRK FUSION; ACQUIRED-RESISTANCE; ALK INHIBITOR; PAN-TRK; ENTRECTINIB; TROPOMYOSIN; MUTATION; ROS1;

D O I：

10.1016/j.cancergen.2022.03.002

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

NTRK fusions drive oncogenesis in a variety of adult cancers. The approval of the first-generation TRK inhibitors, larotrectinib and entrectinib, for any cancer with an NTRK fusion represented a focal point in tumor-agnostic drug development. These agents achieve high response rates and durable disease control, and display intracranial activity. The use of these agents has resulted in a deeper understanding of the clinical consequences of TRK inhibition. These on-target side effects include dizziness, weight gain, and withdrawal pain. The study of TRK inhibitor resistance led to the development of next generation drugs, such as selitrectinib, repotrectinib, taletrectinib, and other agents that maintain disease control against selected acquired kinase domain mutations. This review discusses the clinical efficacy of TRK inhibitors, their safety profiles, and resistance mechanisms with a focus on data in adult cancers.(c) 2022 Elsevier Inc. All rights reserved.

引用

页码：33 / 39

页数：7

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