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REVIEW article

Front. Oncol.
Sec. Breast Cancer
Volume 14 - 2024 | doi: 10.3389/fonc.2024.1427228

REThinking the Role of the RET Oncogene in Breast Cancer

Provisionally accepted
Giuseppe Di Grazia Giuseppe Di Grazia 1Chiara Conti Chiara Conti 1Sabrina Nucera Sabrina Nucera 1Gianmarco Motta Gianmarco Motta 2,3Federica Martorana Federica Martorana 2,3*Stefania Stella Stefania Stella 2Michele Massimino Michele Massimino 4Mario Giuliano Mario Giuliano 5Paolo Vigneri Paolo Vigneri 2,3
  • 1 Department of Human Pathology in Adulthood and Childhood Gaetano Barresi, University of Messina, Messina, Sicily, Italy
  • 2 Department of Clinical and Experimental Medicine, University of Catania, Catania, Sicily, Italy
  • 3 University Oncology, Humanitas Centro Catanese di Oncologia, Catania, Sicily, Italy
  • 4 Department of General Surgery and Medical Surgical Specialties, Policlinico San Marco, Catania, Sicily, Italy
  • 5 Department of Clinical Medicine and Surgery, School of Medicine and Surgery, University of Naples Federico II, Naples, Campania, Italy

The final, formatted version of the article will be published soon.

    The REarranged during Transfection (RET) receptor tyrosine kinase plays a crucial role in the development of various anatomical structures during embryogenesis and it is involved in many physiological cellular processes. This protein is also associated with the initiation of various cancer types, such as thyroid cancer, non-small cell lung cancer, and multiple endocrine neoplasms. In breast cancer, and especially in the estrogen receptor-positive (ER+) subtype, the activity of RET is of notable importance. Indeed, RET seems to be involved in tumor progression, resistance to therapies, and cellular proliferation. Nevertheless, the ways RET alterations could impact the prognosis of breast cancer and its response to treatment remain only partially elucidated. Several inhibitors of RET kinase have been developed thus far, with various degrees of selectivity towards RET inhibition. These molecules showed notable efficacy in the treatment of RET-driven tumors, including some breast cancer cases. Despite these encouraging results, further investigation is needed to fully understand the potential role RET inhibition in breast cancer. This review aims to recapitulate the existing evidence about the role of RET oncogene in breast cancer, from its pathogenic and potentially prognostic role, to the clinical applications of RET inhibitors.

    Keywords: breast cancer, Ret oncogene, targeted therapy, clinical trials, TKI - tyrosine kinase inhibitor

    Received: 03 May 2024; Accepted: 19 Jul 2024.

    Copyright: © 2024 Di Grazia, Conti, Nucera, Motta, Martorana, Stella, Massimino, Giuliano and Vigneri. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Federica Martorana, Department of Clinical and Experimental Medicine, University of Catania, Catania, 95131, Sicily, Italy

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.