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Author Spotlight: Advancing 3D Modeling for Enhanced Diagnosis and Treatment of Pulmonary Nodules in Early-Stage Lung Cancer
Published on: October 13, 2023
Decade in review: a new era for RET-rearranged lung cancers
Noura J Choudhury1, Alexander Drilon1,2
1Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Abstract:
Targeted therapy has become the standard of care for non-small cell lung cancers with a range of targetable alterations, including ALK and ROS1 kinase fusions. RET fusions drive the oncogenesis of 1-2% of NSCLCs and represent a substantial global burden of disease. Although these fusions were first identified more than thirty years ago, targeted therapy for RET fusion-positive lung cancers was only explored in the last decade. Whereas repurposed multikinase inhibitors were initially tested, selective inhibitors RET inhibitors have dramatically improved outcomes for patients whose tumors harbor these alterations. In 2020, the US Food and Drug Administration approved selpercatinib, a selective RET inhibitor, for adults with lung and thyroid cancers with RET rearrangements or mutations, making it the first targeted therapy to be approved for RET-altered cancers. While resistance to selective RET inhibition has been described, next-generation RET inhibitors are already being explored for patients who progress on prior RET kinase inhibitors.
Insights
Targeted therapies, including selective RET inhibitors, have transformed non-small cell lung cancer (NSCLC) treatment. Research is ongoing for next-generation inhibitors to overcome resistance in RET fusion-positive lung cancers.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Non-small cell lung cancer (NSCLC) treatment has advanced with targeted therapies for specific genetic alterations.
- RET fusions are oncogenic drivers in 1-2% of NSCLCs, posing a significant global health challenge.
- Historically, RET fusions were difficult to target, but recent advancements have enabled effective therapies.
Purpose of the Study:
- To review the evolution and impact of targeted therapies for RET fusion-positive NSCLC.
- To highlight the significance of selective RET inhibitors in improving patient outcomes.
- To discuss the emergence of resistance and the development of next-generation inhibitors.
Main Methods:
- Literature review of studies on targeted therapy in NSCLC.
- Analysis of clinical trial data for RET inhibitors.
- Examination of mechanisms of resistance to selective RET inhibition.
Main Results:
- Selective RET inhibitors have significantly improved outcomes for patients with RET fusion-positive NSCLC.
- Selpercatinib, a selective RET inhibitor, was approved in 2020 for RET-altered cancers.
- Resistance to current selective RET inhibitors has been observed, necessitating further research.
Conclusions:
- Targeted therapy, particularly selective RET inhibitors, represents a paradigm shift in treating RET fusion-positive NSCLC.
- The development of next-generation RET inhibitors is crucial for managing acquired resistance.
- Continued research into RET-altered cancers promises further therapeutic advancements.
