Department of Oncology, The First Affiliated Hospital of Chongqing Medical University, 1 Youyi Road, Yuzhong, Chongqing 400016, China.
Department of Radiotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, China.
Molecules. 2022 Dec 13;27(24):8839. doi: 10.3390/molecules27248839.
The well-known proto-oncogene rearrangement during transfection (RET), also known as ret proto-oncogene Homo sapiens (human), is a rare gene that is involved in the physiological development of some organ systems and can activate various cancers, such as non-small cell lung cancer, thyroid cancer, and papillary thyroid cancer. In the past few years, cancers with RET alterations have been treated with multikinase inhibitors (MKIs). However, because of off-target effects, these MKIs have developed drug resistance and some unacceptable adverse effects. Therefore, these MKIs are limited in their clinical application. Thus, the novel highly potent and RET-specific inhibitors selpercatinib and pralsetinib have been accelerated for approval by the Food and Drug Administration (FDA), and clinical trials of TPX-0046 and zetletinib are underway. It is well tolerated and a potential therapeutic for RET-altered cancers. Thus, we will focus on current state-of-the-art therapeutics with these novel RET inhibitors and show their efficacy and safety in therapy.
已知在转染过程中存在原癌基因重排（RET），也称为人类 RET 原癌基因，这是一种罕见的基因，参与某些器官系统的生理发育，并能激活多种癌症，如非小细胞肺癌、甲状腺癌和甲状腺乳头状癌。在过去的几年中，具有 RET 改变的癌症已经用多激酶抑制剂（MKIs）治疗。然而，由于脱靶效应，这些 MKIs 已经产生了耐药性和一些不可接受的不良反应。因此，这些 MKIs 在临床应用中受到限制。因此，新型高效且针对 RET 的抑制剂塞尔帕替尼和普拉替尼已被加速获得美国食品和药物管理局（FDA）的批准，TPX-0046 和泽替替尼的临床试验正在进行中。它具有良好的耐受性，是治疗 RET 改变的癌症的一种潜在治疗方法。因此，我们将重点关注这些新型 RET 抑制剂的最新治疗方法，并展示它们在治疗中的疗效和安全性。
