Kenneth Olive
Columbia University, NY·Pharmacology
Pancreatic ductal adenocarcinoma (PDAC), the most common pancreatic cancer, kills over 52,000 people a year in the U.S. It resists chemotherapy, targeted drugs and immunotherapy.
- Fields
Pharmacology
Biology
Medicine & Clinical Research
- Topics
pancreatic cancer
pancreatic ductal adenocarcinoma
pan-RAS inhibitor
- Grants
- 5 known grants, through Apr 2031
What they work on
- Trace how genetic resistance to pan-RAS inhibitors such as RMC-7977 evolves in pancreatic tumors, including MYC copy number gains, using mouse and human models and clinical trial samples, and identify new vulnerabilities it creates.
- Test whether blocking primary cilia formation or cilia-driven Hedgehog survival signaling overcomes early tumor adaptation and strengthens pan-RAS inhibition in KPC mice.
- Identify which tumor, fibroblast and macrophage subtypes respond to combined MEK/autophagy inhibition, using single-cell RNA sequencing and regulatory network analysis of transcription factor activity across mice, xenografts, explants and trial samples.
- Find new drug combinations that strengthen MEK/autophagy inhibition by targeting the transcription factors that drive each cell type's response to treatment.
- Reconstruct 'paracrine cascades', chains of signals passed between cell types in the pancreatic tumor environment, using network algorithms on matched patient tumor, interstitial fluid, blood and spleen samples.
- Test a Hedgehog-linked pathway connecting myofibroblasts to immune-suppressing myeloid cells and killer lymphocytes, using intact human tumor explants.
- Compare blocking the cystine importer system xC– with destroying cystine using the enzyme cyst(e)inase as ways to trigger ferroptosis in genetically engineered pancreatic cancer mice.
- Test whether coenzyme A taken up via ENPP proteins protects tumors from ferroptosis, and whether MEK inhibition-driven autophagy that frees iron from ferritin sensitizes them to cysteine depletion.
More about the research
About 94–95% of cases are driven by mutations in KRAS, a gene that acts as a growth switch, yet tumors often find ways around drugs aimed at that switch. The research asks how pancreatic tumors survive and adapt to treatment, and how to defeat those escape routes. It draws on several model systems. These include KPC mice, genetically engineered to develop pancreatic cancer, and human tumors grown in mice. The lab also developed tumor 'explants', which are fresh slices of human or mouse tumor kept alive intact for up to a week, alongside clinical trial samples and computational network analysis.
Why it matters
Pancreatic cancer is among the deadliest cancers and responds poorly to current treatments. By revealing how tumors resist pan-RAS and MEK/autophagy inhibitors, how the surrounding tissue protects them, and how to trigger ferroptosis, this work could lead to drug combinations that keep tumors from escaping therapy. Such combinations could help patients whose pancreatic cancer does not respond to chemotherapy.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Shi-He Liu
University of Toledo, OH·Biomedical Engineering
Evaluate whether exosomes displaying both the tumor-homing peptide RGD and the CD47 "don't eat me" peptide on surface protein CD9 (ExoSmart) target pancreatic cancer, using stroma-rich 3D human tumor spheroids in vitro and in vivo.
Wantong Yao
University of Texas MD Anderson Cancer Center, TX·Medicine & Clinical Research
Define the molecular pathways through which a newly identified stress-response regulator helps pancreatic ductal adenocarcinoma (PDAC) cells survive nutrient shortage, low oxygen and oxidative stress, and evade the immune system.
Saunjoo Yoon
University of Florida, FL·Pharmacology
Test the effectiveness of 4NSGnpcetu, anti-EGFR antibody-coated nanoparticles carrying a modified gemcitabine, in patient-derived pancreatic cancer organoids with stroma and in primary tumor cells from patients.
The school
Columbia University: 89 labs on PI Pages, $1.4B a year on research, 625 research doctorates a year.
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