Knight Cancer Research Development Awardee: Sophia Bornstein, MD, PhD

Sophia Bornstein, MD, PhD,  Resident PGY3, Radiation Medicine

Oregon Cancer Ski Out Cancer Research Development Award

Title: "Functional Significance of Tumor-initiating Cells in Recurrent Head and Neck Squamous Cell Carcinoma"

Abstract: Recurrent head and neck squamous cell carcinoma (HNSCC) carries a dismal prognosis, similar to that of metastatic disease, of 10.1 months with optimal therapy. Currently, it is not known what cells are responsible for recurrence after multimodality therapy i.e. surgery, radiation, chemotherapy. Most cells are often effectively treated with current chemotherapy and radiation. Tumors shrink after treatment, but certain treatment-resistant cells often grow back, causing damage to critical structures in the head and neck. Recurrent disease often leads to patient demise. Cells termed tumor-initiating cells (TICs), also known as cancer stem cells, are a small subset of tumor cells thought to be resistant to treatment and responsible for recurrent disease. Therapeutic targeting of these resistant and aggressive cells has the promise of preventing recurrent and metastatic disease. TICs depend on a supportive environment (or niche) to survive. Alterations in proteins surrounding the TICs are theorized to be required for their persistence. Targeting of this supportive mesh is another avenue for therapeutic targeting of TICs. The first aim of this proposal uses a mouse model to show that radiation-treated TICs persist after treatment and are more aggressive due to molecular changes induced by radiation. The second aim uses a prefabricated protein environment in a combinatorial format (microenvironment array) to determine which proteins are important for TIC persistence and survival. Dual targeting of both TIC and microenvironment molecular alterations could improve therapeutic efficacy and the prognosis of recurrent HNSCC.

Co-investigators: Melissa Hirose Wong, PhD, OHSU; Joe Gray, PhD, OHSU; Charles R Thomas, Jr, MD, OHSU

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