Featuring
Vlad Sandulache
Associate Professor, Baylor College of Medicine
MPI, ARTNet H-CARR U 54 Center
Dr. Sandulache is a clinician-scientist studying head and neck cancer, with a focus on treatment resistance, tumor metabolism, oxidative stress, and the biological mechanisms that determine how tumors respond to radiation and chemotherapy.
Hosted by
David Goodrich
Professor, Roswell Park Comprehensive Cancer Center
ARTNet Coordinating and Data Management Center
Dr. Goodrich leads discussions exploring the science, collaboration, and translational impact of cancer resistance research across the ARTNet Consortium.
Episode Summary
The conversation explores how resistance to cancer therapy may begin long before treatment starts. Dr. Sandulache discusses how head and neck tumors can be shaped by selective pressures,including metabolism, oxidative stress, environmental exposures, and immune interactions,that may precondition cancer cells to withstand radiation and chemotherapy. This perspective challenges the traditional distinction between innate and acquired resistance, suggesting that tumor evolution before treatment can profoundly influence therapeutic response.
The discussion highlights oxidative stress as a key driver of this preconditioning and explores the NRF2 pathway as an important mechanism through which tumor cells build antioxidant defenses and become resistant to therapies such as cisplatin and radiation. Dr. Sandulache also discusses opportunities to identify resistant tumors before treatment using transcriptional biomarkers, tumor biopsies, circulating DNA, and metabolic imaging, potentially allowing treatment to be tailored according to a tumor’s resistance profile.
The episode also emphasizes the value of team science within ARTNet, where investigators studying different cancers, therapies, and resistance mechanisms can bring complementary expertise to shared questions.
Key Takeaways
- Treatment resistance may be shaped long before cancer therapy begins
- Metabolic and environmental oxidative stress can precondition tumors to withstand radiation and chemotherapy
- The distinction between innate and acquired resistance may be less clear than traditionally assumed
- NRF2-driven antioxidant defenses may play an important role in resistance to oxidative stress-based therapies
- Transcriptional biomarkers and emerging technologies may help identify resistant tumors before treatment
- Understanding pretreatment tumor biology could enable treatment escalation for resistant disease and de-escalation for sensitive disease
- Cross-disciplinary collaboration within ARTNet helps reveal resistance mechanisms that may apply across different cancer types
