The Emerging Role of RET Alteration in Solid Tumors: From Pathogenesis to Targeted Therapies

Mataji, Maedeh; Ramezaninejad, Soodeh; Sheikholeslami, Seyed Amir; Hosseini, ‏Motahareh; Salari, Sina

doi:10.22034/atj.2025.499637.1003

The Emerging Role of RET Alteration in Solid Tumors: From Pathogenesis to Targeted Therapies

Reviewers

Authors

Maedeh Mataji ¹

Soodeh Ramezaninejad ¹

Seyed Amir Sheikholeslami ²

‏Motahareh Hosseini ³

Sina Salari ⁴

¹ Hematology and Oncology fellowship, Taleghani Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

² Department of Medical Oncology- Hematology,Imam hosein hospital, Shahid beheshti university of medical sciences, Tehran, iran

³ Department of Internal medicine, Taleghani hospital, Shahid beheshti university of medical sciences, Tehran, Iran.

⁴ Department of Medical Oncology-Hematology, Taleghani Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

10.22034/atj.2025.499637.1003

Abstract

The study investigates the emerging role of RET (rearranged during transfection) alterations in solid tumors, focusing on their pathogenesis and implications for targeted therapies. Ret alterations have been proven to be critical oncogenic factors in various types of solid tumors, most notably PTC and NSCLC. These alterations cause continuous activity of RET signaling pathways, contributing to tumor proliferation and progression. A comprehensive review of recent literature was conducted to elucidate the mechanisms by which RET alterations promote oncogenesis across different tumor types. The efficacy of targeted therapies, specifically RET- selective TKIs such as selpercatinib and pralsetinib, was also evaluated through clinical trial data. In conclusion, RET alterations represent a promising target for precision oncology in solid tumors. Continued research is essential to fully understand the genomic landscape of RET-positive cancers and to optimize therapeutic approaches. The findings support the integration of RET testing in clinical practice to facilitate the development of personalized treatment plans for affected patients.

Keywords

RET alterations

solid tumors

Targeted therapy

Tyrosine kinase inhibitors

Precision medicine