Treatment of non-small cell lung cancer with RET rearrangements
- Author(s)
- Hoe, HJ; Solomon, BJ;
- Details
- Publication Year 2025-03-15,Volume 131,Issue #Suppl 1,Page e35779
- Journal Title
- Cancer
- Publication Type
- Review
- Abstract
- Aberrant activation of the RET oncogene by mutations or gene fusions drives various malignancies, including 1%-2% of all non-small cell lung cancers (NSCLCs) that harbor RET gene fusions. Initial attempts to target RET fusion-positive NSCLC with poorly selective multikinase RET inhibitors were associated with significant toxicities and limited efficacy. Two highly potent and selective RET small-molecule inhibitors, selpercatinib and pralsetinib, were granted accelerated approval for advanced RET fusion-positive NSCLC by the US Food and Drug Administration, and have been shown to be highly effective both in treatment-naive and previously treated patients with NSCLC. Selpercatinib has shown superiority over chemotherapy in a phase 3 study (LIBRETTO-431) in previously untreated patients with RET fusion-positive NSCLC, which established its place as the standard of care in this patient population. This review discusses the biology and clinical characteristics of RET-rearranged NSCLC and summarizes the evolution of treatment strategies, current understanding of mechanisms of resistance, and development of new-generation agents to overcome resistance.
- Publisher
- Wiley
- Keywords
- Humans; *Carcinoma, Non-Small-Cell Lung/genetics/drug therapy/pathology; *Proto-Oncogene Proteins c-ret/genetics/antagonists & inhibitors; *Lung Neoplasms/genetics/drug therapy/pathology; *Gene Rearrangement; Protein Kinase Inhibitors/therapeutic use; Pyrazoles/therapeutic use; Drug Resistance, Neoplasm/genetics; Pyridines/therapeutic use; Pyrimidines; Ret; Ret nsclc; RET fusion; RET rearrangements; lung cancer; non–small cell lung cancer (NSCLC); pralsetinib; selpercatinib
- Department(s)
- Medical Oncology
- Publisher's Version
- https://doi.org/10.1002/cncr.35779
- Open Access at Publisher's Site
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Creation Date: 2025-04-15 07:53:05
Last Modified: 2025-04-15 07:53:18