Prevalence and Actionability of MTAP Loss in Oncogene-Driven Lung Cancer.

ABSTRACT:

Background

Methylthioadenosine phosphorylase (MTAP) loss co-occurs with actionable genomic alterations in non-small cell lung cancer (NSCLC) and creates vulnerability to protein arginine methyltransferase 5 (PRMT5) inhibition. Estimates of prevalence of MTAP loss rely on next-generation sequencing which can underestimate copy losses. Moreover, the activity of PRMT5 inhibitors in oncogene-driven NSCLC is not well established.

Methods

We assessed MTAP expression by immunohistochemistry (IHC) in 243 NSCLCs (n=132 early stage, n=111 metastatic), including 33 specimens with paired lymph nodes. Antiproliferative activity of PRMT5 inhibitor monotherapy and in combination with tyrosine kinase inhibitors (TKIs) was evaluated in MTAP-deleted NSCLC cell lines harboring EGFR or <

SUBMITTER: Sakai T 

PROVIDER: S-EPMC12871827 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature