Rearranged during transfection (RET) lung cancer - Update on targeted therapies

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Non-small cell lung cancer (NSCLC) oncogenesis involves complex molecular pathways.
• The rearranged during transfection (RET) proto-oncogene plays a role in development and is implicated in 1-2% of NSCLC cases.
• Targeted therapies have advanced personalized treatment for NSCLC with actionable mutations.

Purpose of the Study:

• To review the progress of targeted therapies for NSCLC with RET alterations.
• To highlight the efficacy and tolerability of selective RET inhibitors (SRIs) compared to multikinase inhibitors (MKIs).
• To discuss ongoing research into next-generation SRIs for overcoming resistance and improving patient outcomes.

Main Methods:

• Literature review of targeted therapies for NSCLC with RET alterations.
• Analysis of clinical trial data for selective RET inhibitors (SRIs) like selpercatinib and pralsetinib.
• Examination of emerging research on next-generation SRIs and their potential applications.

Main Results:

• Selective RET inhibitors (SRIs) have significantly improved patient outcomes in NSCLC with RET fusions, offering deep and durable responses.
• SRIs demonstrate superior efficacy and tolerability compared to older multikinase inhibitors (MKIs).
• Clinical trials are investigating the use of SRIs in neoadjuvant and adjuvant settings.

Conclusions:

• Selective RET inhibitors (SRIs) represent a major advancement in personalized medicine for NSCLC patients with RET alterations.
• Next-generation SRIs are under development to address resistance mechanisms and further enhance treatment efficacy and safety.
• Continued research in targeted therapies holds promise for improving long-term outcomes in NSCLC.