Interplay of tumor genomic and immune characteristics and external drivers of health to improve cancer health outcomes

The overall goal of the UCSF SPORE is to improve cancer health outcomes by investigating the interplay of genomic and immune characteristics with individual risk factors and external drivers of health. Three cancers (meningioma, prostate cancer and breast cancer) with well-known differences related to clinical outcomes, will be studied. At the heart of the proposal are three translational research projects—each intended to evaluate novel tools and models to examine the interplay of external drivers and the biology of the disease with defined human endpoints. Project 1 aims to understand meningioma outcome differences between Black and White individuals in the context of external factors and individual-level risk factors using human samples, bioinformatics, preclinical models, and epidemiological data. Project 2 will characterize, at an unprecedented detail and depth, the explanatory variables, both biological (genomic) and environmental and individual lifestyle parameters, that explain prostate cancer outcome differences, with a particular focus on the complex interactions among stress and inflammation within across different populations. The response of the immune system to breast cancer therapy is a major determinant of breast cancer outcomes and the tumor immune microenvironment (TME) varies substantially among different populations. The goal of Project 3 is to identify the genetic and environmental factors that underlie these differences and to understand the underlying pathway mechanisms. Each Project is led by a balanced representation across basic and applied/clinical research investigators with critical involvement from biostatistical experts working with epidemiological scientists to ensure scientific rigor of the research strategy. Cancer surgeons are also integral to the projects. The Developmental Research and Career Enhancement Programs are vital to the expansion of research opportunities that will foster and build on a strong community of qualified investigators across the HDFCCC. The projects and programs will be supported by 3 specialized Cores (Administrative, Biospecimen and Pathology, and Community Outreach and Engagement). Research progress and scientific direction will be evaluated by the Executive Committee of the SPORE (all leaders and directors) with the expert guidance of the Internal and External Advisory Boards. In addition to leveraging the multidisciplinary expertise within the research programs in the UCSF HDFCCC, the 3 established UCSF SPORE grants in Brain, Prostate Cancer and Developmental Hyper-Ras Tumors (DHART) and the incredible resources from the institution, this SPORE will benefit greatly from rich collaborations with investigators at outside institutions and the Community Advisory Board members. The work proposed under this grant will yield valuable insights and make meaningful progress in understanding and reducing health outcome differences related to patients with meningioma, prostate cancer and breast cancer respectively.