2025 Cancer Outcomes SPORE

Overview

Translational Research Program in Cancer Outcomes Across Populations

This program is funded by an NCI Specialized Program of Research Excellence (SPORE) grant and supported by the UCSF Helen Diller Family Comprehensive Cancer Center, the Departments of Neurological Surgery and Urology, and the Breast Oncology Program.

The SPORE aims to improve cancer health outcomes across populations by investigating the interplay of tumor biology with individual risk factors and external drivers of health. The grant focuses on studying three types of cancer with well-known differences in clinical outcomes: meningioma, prostate cancer, and breast cancer.

The SPORE grant, led by Susan Chang, MD, with co-director Franklin Huang, MD, PhD, supports three translational research projects (described below) and three resource cores. The Administrative Core (Leaders: Susan Chang, MD, Franklin Huang, MD, PhD, and Co-I David Raleigh MD, PhD) supervises the activities of the program while the Biospecimen/Pathology Core (Leaders Joanna Phillips, MD, PhD, Cornelia Ding, MD, PhD, and Alexander Borowsky, MD, PhD) and the Community Outreach/Engagement (Leaders: Samuel Washington, MD, Scarlett Gomez, PhD, MPH) provide specialized expertise in service of the main research projects. The Career Enhancement Program, managed by Shawn Hervey-Jumper, MD, provides support for early career investigators, and the Developmental Research Program, managed by Iona Cheng, PhD, supports innovative high-risk, high-reward pilot projects. A multidisciplinary team of internal and external scientific advisors, patient advocates and the members of the Community Advisory Board, provide overall guidance on the direction of the SPORE.

Projects

Genomic and biochemical mechanisms underlying differences in meningioma outcomes

Many high-grade meningiomas (grades 2 and 3) are resistant to currently available treatments with surgery and radiotherapy. Using data from the Central Brain Tumor Registry of the United States, we have found that these tumors with higher recurrence rates are more common in some patient populations. The tumors from these patients also have molecular features consistent with more aggressive disease. We hypothesize that the interaction between tumor biology, external drivers, and individual risk factors underlies these differences in meningioma incidence and disease burden. This project aims to establish the generalizability of DNA methylation and gene expression biomarkers for managing disease across all patient populations. The project leverages rich collaborations with investigators from the University of Alabama, Birmingham, Northwestern University, Duke University and Baylor College of Medicine.

Led by David Raleigh, MD, PhD, and Nancy Ann Oberheim Bush, MD, PhD, this project will:

• Define the molecular architecture of meningiomas across external drivers and personal risk factors
• Identify the role that a progesterone receptor protein (PGRMC1) plays in driving meningioma growth
• Develop new therapies to block the PGRMC1

Elucidating interactions between genetic and environmental drivers of prostate cancer outcomes

Some patient populations face a higher burden of more aggressive, deadly prostate cancer. This research studies how both genetic and environmental factors contribute to these differences in patient outcomes. The project focuses on the interactions between stress, inflammation, and immune pathways within the tumor microenvironment.

Led by Franklin Huang, MD, PhD, and Matthew Cooperberg, MD, with co-investigators Li Zhang, William Chen and David Quigley, in collaboration with investigators from Boston University,  this project will:

• Identify how adverse external factors drive differences in immune activation and the development of more aggressive types of prostate cancer
• Create a comprehensive molecular atlas that maps the immune cell profiles in prostate cancer across populations
• Develop machine learning models to predict which men are at the highest risk for aggressive prostate cancer

Understanding the drivers of response-predictive inflammatory states underlying differences in health outcomes in patients with breast cancer

The tumor immune microenvironment influences patient outcomes for many tumors, including breast cancer. Many features of the tumor immune microenvironment vary across different populations. This project studies how genomic variants and combinations of variants – called polygenic risk scores – affect the tumor immune microenvironment and contribute to differences in treatment response.

Led by Jennifer Rosenbluth, MD, PhD, and Elad Ziv, MD, with co-investigators Kimberly Badal, PhD, and Rosalyn Sayaman, PhD, and colleagues at City of Hope, this project aims to:

• Determine whether genetic variants underlie differences in treatment response through differences in tumor immune signatures
• Identify the specific tumor immune microenvironment pathways by which inherited genetic factors affect response to targeted treatments, chemotherapy agents, and immunotherapies
• Examine whether differences in exposure to adverse external factors across patient populations influence the tumor immune microenvironment and predict breast cancer recurrence and treatment response

For more information, contact administrator Felicia Widjaja ([email protected]).