Head and Neck Cancer SPORE

PROJECT SUMMARY – OVERALL For more than 15 years, the UPMC Hillman Cancer Center (HCC) Head and Neck SPORE has facilitated practice change in diagnosis and treatment of head and neck squamous cell carcinomas (HNSCC) and other head and neck cancers. For the renewal period, the SPORE will focus on the remaining problems of debilitating toxicities, low immunotherapy response rates, and the need for precision oncology in HNSCC treatment. Through its multidisciplinary project teams, four clinical trials, and analysis of a completed clinical trial, the SPORE will investigate: 1) how hypoxia and metabolic dysregulation leads to PD-1 immunotherapy resistance and how it can be overcome, 2) how patients with human papillomavirus-positive oropharyngeal cancers can be optimally selected for deintensified therapy, and 3) which biomarkers can be used for predicting responsiveness to combined immunotherapy with PD-1 and LAG3 inhibitors. The studies will be conducted with the support of state-of-the-art Cores that provide access to over 6,400 well-characterized, clinically annotated biospecimens; biostatistical and bioinformatics support; and advanced technology platforms that include multiplexed cytometry and imaging, next generation and single sequencing; and radiomic and radiogenomic analyses based on features extracted from patient CT scans. Through the SPORE’s Developmental Research Program (DRP) and Career Enhancement Program (CEP), translational head and neck cancer research will be further advanced with new ideas, research strategies, and investigators. These programs will focus heavily on increasing diversity by attracting and advancing projects from woman and underrepresented minorities groups via internal initiatives and external collaborations. Critical to the success of the research is the wealth of longitudinal clinical data collected on nearly 12,000 patients with longitudinal 30 years’ of clinical follow up in the SPORE’s Organ Specific Database (OSD), which is now been expanded to include quality of life measures, as well as extensive genomics, radiomics and transcriptomic data. Established horizontal and vertical collaborations with other Cancer Centers, national cooperative trial groups, industrial partners enable and extend the efforts of the SPORE investigators. Submission of this renewal application was intentionally taken off cycle, separating its renewal cycle from the HCC CCSG P30, to maximize institutional resources that could be devoted to both applications, as well as to provide additional time for newly recruited SPORE leaders to collaborate and solidify their interactions as a team at HCC. HCC’s has continued to support the HN SPORE, including soliciting CEP and DRP awards, highlight its strong commitment to its renewal.