Verrienti Antonella, Grani Giorgio, Sponziello Marialuisa, Pecce Valeria, Damante Giuseppe, Durante Cosimo, Russo Diego, Filetti Sebastiano
Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy.
Department of Medicine, University of Udine, Udine, Italy.
Front Oncol. 2022 Aug 24;12:992636. doi: 10.3389/fonc.2022.992636. eCollection 2022.
Aberrant activation of the proto-oncogene is implicated in a plethora of cancers. gain-of-function point mutations are driver events in multiple endocrine neoplasia 2 (MEN2) syndrome and in sporadic medullary thyroid cancer, while rearrangements are driver events in several non-medullary thyroid cancers. Drugs able to inhibit RET have been used to treat -mutated cancers. Multikinase inhibitors were initially used, though they showed modest efficacy and significant toxicity. However, new RET selective inhibitors, such as selpercatinib and pralsetinib, have recently been tested and have shown good efficacy and tolerability, even if no direct comparison is yet available between multikinase and selective inhibitors. The advent of high-throughput technology has identified cancers with rare alterations beyond point mutations and fusions, including deletions, raising questions about whether these alterations have a functional effect and can be targeted by RET inhibitors. In this mini review, we focus on tumors with deletions, including deletions/insertions (indels), and their response to RET inhibitors.
原癌基因的异常激活与多种癌症有关。功能获得性点突变是多发性内分泌肿瘤2型（MEN2）综合征和散发性甲状腺髓样癌的驱动事件，而重排是几种非甲状腺髓样癌的驱动事件。能够抑制RET的药物已被用于治疗RET突变的癌症。最初使用的是多激酶抑制剂，但其疗效一般且毒性较大。然而，新的RET选择性抑制剂，如塞尔帕替尼和普拉替尼，最近已进行了测试，显示出良好的疗效和耐受性，尽管目前多激酶抑制剂和选择性抑制剂之间尚无直接比较。高通量技术的出现已鉴定出除点突变和融合外具有罕见改变的癌症，包括缺失，这引发了关于这些改变是否具有功能效应以及是否可被RET抑制剂靶向的问题。在本综述中，我们重点关注具有缺失（包括缺失/插入，即Indel）的肿瘤及其对RET抑制剂的反应。
