CONICET-UBA, Instituto de Fisiología, Biología Molecular y Neurociencias (IFIBYNE), Ciudad Universitaria, C1428EGA CABA, Buenos Aires, Argentina.
Universidad de Buenos Aires (UBA), Facultad de Ciencias Exactas y Naturales, Ciudad Universitaria C1428EGA CABA, Buenos Aires, Argentina.
J Mammary Gland Biol Neoplasia. 2020 Mar;25(1):13-26. doi: 10.1007/s10911-020-09445-4. Epub 2020 Feb 21.
Ret receptor tyrosine kinase is a proto-oncogene that participates in development of various cancers. Several independent studies have recently identified Ret as a key player in breast cancer. Although Ret overexpression and function have been under investigation, mainly in estrogen receptor positive breast cancer, a more comprehensive analysis of the impact of recurring Ret alterations in breast cancer is needed. This review consolidates the current knowledge of Ret alterations and their potential effects in breast cancer. We discuss and integrate data on Ret changes in different breast cancer subtypes and potential function in progression, as well as the participation of distinct Ret network signaling partners in these processes. We propose that it will be essential to define a shared molecular feature of tumors with alteration in Ret receptor, be this at the genetic level or via overexpression in order to design effective therapies to target the Ret pathway. Here we review experimental evidence from basic research and pre-clinical studies concentrating on Ret alterations as potential biomarkers for recurrence, and we discuss the possibility that targeting the Ret pathway might in the future become a treatment for breast cancer.
Ret 受体酪氨酸激酶是一种原癌基因，参与多种癌症的发生。最近有几项独立的研究表明 Ret 是乳腺癌的关键因素。虽然 Ret 的过表达和功能已经在研究中，主要是在雌激素受体阳性的乳腺癌中，但需要对乳腺癌中复发性 Ret 改变的影响进行更全面的分析。这篇综述总结了 Ret 改变及其在乳腺癌中的潜在作用的现有知识。我们讨论并整合了不同乳腺癌亚型中 Ret 变化的数据及其在进展中的潜在功能，以及不同 Ret 网络信号伙伴在这些过程中的参与。我们提出，为了设计针对 Ret 途径的有效治疗方法，定义具有 Ret 受体改变的肿瘤的共同分子特征至关重要，无论是在遗传水平上还是通过过表达。在这里，我们回顾了基础研究和临床前研究的实验证据，集中讨论了 Ret 改变作为复发的潜在生物标志物的可能性，并讨论了将来靶向 Ret 途径可能成为治疗乳腺癌的一种方法。
