Harnessing Nutritional Modulation to Enhance Cancer Drug Potency

Abstract public domain (NIH RePORTER)

Summary Effective treatment of advanced cancers remains a major challenge due to therapy resistance and limited response rates. This proposal aims to develop a genetic screening approach to systematically identify and exploit drug-diet interactions that enhance cancer therapy efficacy by leveraging cancer- specific metabolic vulnerabilities. By integrating precision dietary interventions with targeted therapies, we seek to improve treatment selectivity, minimize side effects, and expand therapeutic options, particularly for aggressive or treatment-resistant cancers. Our approach is based on the premise that cancer cells exhibit distinct metabolic dependencies, which can be exacerbated under diet-induced metabolic stress. We propose to establish an unbiased, parallel screening platform using syngeneic orthotopic pancreatic ductal adenocarcinoma (PDAC) models to evaluate the interaction of over 2,000 drug targets with a defined dietary intervention that affects cancer cell proliferation. Promising drug-diet synergies identified from this screen will be further validated by assessing the impact of diet on drug efficacy in vivo. By focusing on clinically relevant compounds and personalized dietary strategies, this research has the potential to rapidly translate into novel combination therapies. The proposed study will provide a foundational framework for leveraging metabolic stress to enhance the effectiveness of existing cancer treatments, paving the way for innovative precision medicine approaches in oncology.

Public health relevance public domain (NIH RePORTER)

Project Narrative Cancer cells exhibit unique metabolic dependencies and depend on signaling pathways that are less critical in normal cells during fluctuating nutrient conditions. This proposal aims to develop and verify a genetic approach to identify synergies between precision diets and cancer drugs.