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Dana-Farber Research News 04.01.2026
This twice-monthly newsletter highlights recently published research where Dana-Farber faculty are listed as first or senior authors. The information is pulled from PubMed and this issue notes papers published from March 1 - 15.
Clinical Report: MTAP Loss in Oncogene-Driven NSCLC and PRMT5 Inhibition
Overview
This report highlights the frequent occurrence of MTAP loss in oncogene-driven non-small cell lung cancers (NSCLCs) and its potential therapeutic implications. The study demonstrates that MTAP loss may confer sensitivity to PRMT5 inhibitors, particularly in combination with targeted therapies.
Background
Understanding the genetic landscape of NSCLC is crucial for developing targeted therapies. MTAP loss occurs in a significant subset of cancers and may create vulnerabilities that can be exploited therapeutically. This study sheds light on the prevalence of MTAP loss in NSCLC and its implications for treatment strategies.
Data Highlights
Oncogenic Driver
MTAP Loss (NGS)
MTAP Loss (IHC)
ALK-rearranged
27% - 33%
36% - 45%
RET-rearranged
18.5% - 26%
35%
EGFR-mutant
17% - 24%
24% - 29%
Key Findings
MTAP loss was found in 27% to 33% of ALK-rearranged NSCLC samples.
MTAP loss occurred in 18.5% to 26% of RET-rearranged NSCLC samples.
In EGFR-mutant NSCLC, MTAP loss was present in 17% to 24% of cases.
MTAP loss was typically present prior to targeted therapy initiation.
BMS-986504 showed nanomolar activity in 11 out of 18 MTAP-deleted models.
Combination therapy with BMS-986504 and targeted therapies improved antitumor activity in resistant models.
Clinical Implications
Clinicians should consider the assessment of MTAP status in patients with oncogene-driven NSCLC to identify potential candidates for PRMT5 inhibitor therapy. The findings suggest that combining PRMT5 inhibitors with existing targeted therapies may enhance treatment efficacy in specific patient populations.
Conclusion
MTAP loss is prevalent in oncogene-driven NSCLC and presents a promising target for therapeutic intervention. Further studies are warranted to explore the clinical utility of PRMT5 inhibitors in this context.
