Donahue Lab
Principal Investigator: Timothy R Donahue
Institution: Cornell University (Ithaca, NY)
Primary Subfield: Molecular & Cell Bio
Recruitment Status: Inquire for rotation/fellowship opportunities
Research Focus
PROJECT SUMMARY Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive forms of cancer, known for its profound immune suppression and resistance to most therapies. One strategy to overcome these barriers is to leverage the effects of standard-of-care chemotherapy to increase extracellular ATP and promote anti-tumor inflammation. However, PDACs express high levels of ectonucleotidases ENPP1, CD39, and CD73 that quickly convert extracellular ATP released by dying tumor cells to immunosuppressive adenosine. In a recent Phase IA/1B clinical trial at UCLA for patients with Borderline Resectable PDAC (NCT03970252), neoadjuvant FOLFIRINOX chemotherapy and PD-1 inhibition produced changes of a more permissive anti-tumor immune microenvironment (TME) and was associated with excellent overall survival. However, compensatory adenosine signaling increased in post-treatment tumors, potentially hindering anti-tumor immunity. To strategically address this problem, a follow-up Phase 1/2 trial (NCT05688215) was initiated at UCLA in collaboration with Arcus Biosciences that introduces a small molecule inhibitor of CD73 to neoadjuvant FOLFIRINOX and PD-1 inhibition to limit adenosine i…
Active NIH Awards
- 5R01CA290888-03: Causes and Consequences of Adenosine Signaling in Pancreatic Cancer (2026)
- 5R01CA290888-02: Causes and Consequences of Adenosine Signaling in Pancreatic Cancer (2025)
- 5R01CA250529-05: Leveraging Vulnerabilities Induced by STING Activation in Pancreatic Cancer (2025)
- 5R01CA250529-04: Leveraging Vulnerabilities Induced by STING Activation in Pancreatic Cancer (2024)
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