Project Summary Patient-derived model systems are commonly used to study tumor biology and test novel treatments for head and neck cancer. Our goal is to improve the use of mammalian model systems of head and neck cancer to improve treatment outcomes for patients using valid, predictive, well characterized models. The goal of this supplement is to study cancer evolution and therapeutic response with rigorous assessment of tumor biology and genomic alterations to understand how choices made at the time of establishing models impact their relevance over time. Aim 1 will assess the role of heterotopic vs. orthotopic implantation on the therapeutic response and biology of the tumor. Aim 2 will test the concordance of response between patient-derived models and patients. We will use this supplement to support a minority graduate student in the medical physics program to study the effect of radiation on tumor evolution, to provide her with additional training in team science, mentoring, teaching, and communication to support her pursuit of an independent research career.