GDC-0941 (pictilisib)
Overview
GDC-0941 (pictilisib) is a potent, selective pan-class I PI3K inhibitor that targets PI3K-alpha, -beta, -delta, and -gamma. It was investigated primarily as a single agent and in combination in solid tumors and hematologic malignancies.
Evidence in the corpus
- PI3K inhibitor GDC-0941 substantially inhibited proliferation of all hypodiploid ALL tumors tested ex vivo (both near haploid and low hypodiploid subtypes), consistent with PI3K pathway dependence in both subtypes; MEK inhibitors were ineffective despite high Ras pathway mutation frequency PMID:23334668.
- Combined PLX4720 (RAF inhibitor) + GDC-0941 (PI3K inhibitor) markedly suppressed proliferation and induced apoptosis in BRAF V600E / PTEN-null A2058 melanoma cells but not in PTEN-WT A375 cells, supporting combination MAPK+PI3K therapy in PTEN-loss contexts PMID:24265153
- Nominated as a candidate PI3K-pathway therapy for the 4% of pancreatic ductal adenocarcinomas carrying activating PIK3CA mutations (mutually exclusive with KRAS), identified by WES of 109 resected PDA cases PMID:25855536
Resistance mechanisms
- MEK inhibition alone was insufficient despite near-universal RAS/MAPK pathway activation in near haploid ALL, suggesting PI3K pathway is the critical downstream effector node PMID:23334668.
Cancer types (linked)
- BLL — hypodiploid ALL (both near haploid and low hypodiploid subtypes); ex vivo sensitivity established.
Sources
This page was processed by crosslinker on 2026-05-14. - PMID:24265153
This page was processed by crosslinker on 2026-05-14. - PMID:25855536
This page was processed by crosslinker on 2026-05-14.