This supplement application proposes to address gaps in our understanding of rare cancers in underrepresented individuals. This proposal is related to the work conducted in the parent grant R01- CA264248, which was designed to develop innovative patient-derived organoid (PDOs) models of rare cancers, neuroendocrine tumors known as pheochromocytomas and paragangliomas (PPGLs). In these tumors progress has lagged due to a dearth of experimental model systems. By generating novel PDOs we aim to address two gaps in PPGLs: 1) early recognition of aggressive disease, and 2) identification of effective treatments. Recent studies have suggested that ethnicity may contribute both to the mutation profile and overall survival of PPGL patients. Certain socioeconomic indicators that can impact on disease features and outcomes can co-associate in underrepresented populations. In this supplement, we will leverage our expertise in generating and evaluating PDOs to establish models from underrepresented racial/ethnic minority patients diagnosed with PPGLs, as well as patients with aggressive forms of PPGLs. We propose to define the patients’ genetic admixture, and evaluate clinical, standardized social determinants of health and how they associate with biomarkers of tumor behavior, genetic selection, and drug response detected in PDOs. To achieve our goals, and recruit this patient population, we will expand our team to include two collaborators with expertise in cancer disparities and clinical care of patients from diverse ethnic backgrounds. Our studies may provide insights into PPGL biology, the prevalence of clinically actionable alterations and potential drug selection for treatment in PDOs from underrepresented patients which can be incorporated onto the design of future studies that address disparities in rare tumors.