Map ferroptosis pathway gene dependencies across all cancer types in DepMap 25Q3, stratified by NRF2/KEAP1 mutation status, to identify which cancer types beyond NSCLC are most susceptible to ferroptosis-inducing therapies (icFSP1, GPX4i, GLS1i). Extends the 5-layer KEAP1-MUT ferroptosis defense model from nsclc-depmap-targets to pan-cancer context.

Determine whether MTAP-deleted NSCLC cell lines show enhanced PRMT5 dependency in DepMap 25Q3, and identify co-mutation contexts (KRAS alleles, STK11, KEAP1, TP53) that modulate this synthetic lethal relationship to guide patient selection for PRMT5 inhibitor trials (IDE892 Phase 1 enrolled March 2026).

Identify actionable therapeutic targets and synthetic lethal pairs in NSCLC by mapping DepMap cancer dependencies to TCGA patient molecular profiles, stratified by oncogenic driver (KP/KL/KOnly) and immune context. Reproduces and extends TCGADEPMAP (Nature Cancer 2024) with DepMap 25Q3, SL integration, PRISM drug mapping, and LUCA scRNA-seq validation.