Expert consensus on the diagnosis and treatment of RET gene fusion non-small cell lung cancer in China

Thorac Cancer. 2023 Nov;14(31):3166-3177. doi: 10.1111/1759-7714.15105. Epub 2023 Sep 18.

Abstract

The rearranged during transfection (RET) gene is one of the receptor tyrosine kinases and cell-surface molecules responsible for transmitting signals that regulate cell growth and differentiation. In non-small cell lung cancer (NSCLC), RET fusion is a rare driver gene alteration associated with a poor prognosis. Fortunately, two selective RET inhibitors (sRETi), namely pralsetinib and selpercatinib, have been approved for treating RET fusion NSCLC due to their remarkable efficacy and safety profiles. These inhibitors have shown the ability to overcome resistance to multikinase inhibitors (MKIs). Furthermore, ongoing clinical trials are investigating several second-generation sRETis that are specifically designed to target solvent front mutations, which pose a challenge for first-generation sRETis. The effective screening of patients is the first crucial step in the clinical application of RET-targeted therapy. Currently, four methods are widely used for detecting gene rearrangements: next-generation sequencing (NGS), reverse transcription-polymerase chain reaction (RT-PCR), fluorescence in situ hybridization (FISH), and immunohistochemistry (IHC). Each of these methods has its advantages and limitations. To streamline the clinical workflow and improve diagnostic and treatment strategies for RET fusion NSCLC, our expert group has reached a consensus. Our objective is to maximize the clinical benefit for patients and promote standardized approaches to RET fusion screening and therapy.

Keywords: NSCLC; RET fusion; precision medicine; targeted therapy; tyrosine receptor kinase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Non-Small-Cell Lung* / diagnosis
  • Carcinoma, Non-Small-Cell Lung* / drug therapy
  • Carcinoma, Non-Small-Cell Lung* / genetics
  • Consensus
  • Gene Fusion
  • Humans
  • In Situ Hybridization, Fluorescence
  • Lung Neoplasms* / diagnosis
  • Lung Neoplasms* / drug therapy
  • Lung Neoplasms* / genetics
  • Proto-Oncogene Proteins c-ret / genetics

Substances

  • Proto-Oncogene Proteins c-ret
  • RET protein, human