Follow the research questions
Select a topic, then explore the publications connected to this work.
Overview
GRIT (GI RAS Innovative Therapeutics) is our lab-led initiative to bring RAS-directed therapy to the full spectrum of gastrointestinal cancers. It grows directly out of the KRAS-driven vulnerabilities program in pancreatic cancer and treats RAS as a shared therapeutic axis across GI histologies.
The initiative unifies target discovery, first-in-class drug development, clinicogenomic profiling, and biomarker-driven trial design under one translational strategy led by Dr. Wungki Park.
Explore the published evidence
Setidegrasib in Advanced Non–Small-Cell Lung Cancer and Pancreatic Cancer
First-in-human phase 1 study of setidegrasib (ASP3082), a first-in-class KRAS G12D targeted protein degrader. Among 21 patients with previously treated metastatic PDAC receiving the 600 mg dose, 24% achieved objective response; median PFS and OS were 3.0 and 10.3 months. In NSCLC (n=45), ORR was 36% with median PFS of 8.3 months.
- ORR 24% (PDAC)
- mPFS 3.0 mo (PDAC)
- Phase 1
Overview
GRIT (GI RAS Innovative Therapeutics) is our lab-led initiative to bring RAS-directed therapy to the full spectrum of gastrointestinal cancers. It grows directly out of the KRAS-driven vulnerabilities program in pancreatic cancer and treats RAS as a shared therapeutic axis across GI histologies.
The initiative unifies target discovery, first-in-class drug development, clinicogenomic profiling, and biomarker-driven trial design under one translational strategy led by Dr. Wungki Park.
The pan-GI RAS thesis
RAS-pathway alterations recur across pancreatic, biliary tract, gastric/gastroesophageal junction, appendiceal, and colorectal cancers, but the allele spectrum, mutant dosage, and co-mutation context differ by histology.
GRIT asks how RAS(ON) inhibitors and targeted degraders — validated first in pancreatic cancer — should be adapted, sequenced, and combined for each GI context, and which genomic determinants predict benefit.
Roadmap
The initiative advances in waves: pancreatic ductal adenocarcinoma (PDAC) first, then biliary tract cancer (BTC), followed by gastric/GEJ, appendiceal, and colorectal cancer.
Each expansion carries forward the same infrastructure — degrader and RAS(ON) therapeutics, next-generation sequencing, ctDNA monitoring, and neoantigen and immune profiling — so that insight in one disease accelerates the next.