Article

Acquired resistance to the PRMT5 inhibitor confers collateral sensitivity to MEK inhibition in MTAP-null non-small cell lung cancer

2026-04-21

Abstract excerpt

Protein arginine methyltransferase 5 (PRMT5) is a synthetic lethal target in methylthioadenosine phosphorylase-deleted (MTAP-null) cancers. Second-generation MTA-cooperative PRMT5 inhibitors preferentially target MTAP-null cells while largely sparing MTAP-wildtype (MTAP-WT) cells, thereby improving tumor selectivity over first-generation PRMT5 inhibitors. Despite encouraging efficacy and safety signals in early cl...

Topics

Open a Topic to create a Post that cites this publication.

Identifiers and source

Literature Corpus work: 29f07503-12c3-50de-a800-f688ad0e85d0
DOI: 10.64898/2026.04.16.719008

Open publication

Related research

Semantic proximity does not establish scientific evidence.

Click a neighbor to travelStep 1 · 12 closest

Acquired resistance to the PRMT5 inhibitor confers collateral sensitivity to MEK inhibition in MTAP-null non-small cell lung cancerDOI 10.64898/2026.04.16.719008Read

Prevalence and Actionability of MTAP Loss in Oncogene-Driven Lung CancerSemantic proximity Read

Genomic landscape of non-small-cell lung cancer with methylthioadenosine phosphorylase (MTAP) deficiency.Semantic proximity Read

Combination of the MTA-Cooperative PRMT5 Inhibitor BMS-986504 and KRAS Inhibitors Is an Effective Treatment Strategy for MTAP-Deleted KRAS-Mutant Pancreatic Cancer.Semantic proximity Read

RAS-MAPK Reactivation Facilitates Acquired Resistance in FGFR1-Amplified Lung Cancer and Underlies a Rationale for Upfront FGFR-MEK Blockade.Semantic proximity Read

Acquired resistance to PRMT5 inhibition induces concomitant collateral sensitivity to paclitaxel.Semantic proximity Read

PRMT5 inhibitors actively promote metastatic progression of lung adenocarcinomaSemantic proximity Read

Clinicogenomic Landscape of MTAP-Deleted Thoracic Malignancies Across US and Japanese Nationwide Cohorts: Impact of Concurrent CDKN2A Alterations and Driver Mutations.Semantic proximity Read

Designing Effective Protein Lysine and Arginine Methyltransferase Inhibitors for Chemotherapeutic TargetingSemantic proximity Read

Resistance is futile: overcoming resistance to targeted therapies in lung adenocarcinomaSemantic proximity Read

PP2A inhibition is a druggable MEK inhibitor resistance mechanism in KRAS-mutant lung cancer cells.Semantic proximity Read

Mediator Kinase Inhibition Impedes Transcriptional Plasticity and Prevents Resistance to ERK/MAPK-Targeted Therapy in KRAS-Mutant CancersSemantic proximity Read

A PP2A molecular glue overcomes RAS/MAPK inhibitor resistance in KRAS-mutant non-small cell lung cancer.Semantic proximity Read