The PCF Challenge Award Winners – Class of 2021 recipients are:
2021 Movember-PCF Challenge Award
Principal Investigators: Franklin Huang, MD, PhD (University of California, San Francisco; San Francisco Veterans Affairs Medical Center), Elisabeth Heath, MD (Karmanos Cancer Institute; Wayne State University), Clayton Yates, PhD (Tuskegee University)
Co-Investigators: Hala Borno, MD (University of California, San Francisco), Matthew Cooperberg, MD, MPH (San Francisco Veterans Affairs Medical Center; University of California, San Francisco), Nancy Greenland, MD, PhD (San Francisco Veterans Affairs Medical Center; University of California, San Francisco), Felix Feng, MD (University of California San Francisco), Thomas Hope, MD (San Francisco Veterans Affairs Medical Center; University of California, San Francisco)
Project Title: MET-PAAM: Elucidating the Molecular Mechanisms of Tumor Progression in Metastatic Prostate Cancer among Men of African Ancestry
- Significant prostate cancer disparities exist for African American (AA) patients, who have a higher overall incidence, earlier age of onset, increased proportion of clinically advanced disease, and increased mortality from prostate cancer compared to European American (EA) patients, even after adjusting for social factors. This suggests that other factors, including differences in tumor biology by race/ethnicity/ancestry may contribute to disparities. Understanding the factors that contribute to prostate cancer disparities in AA patients is of critical importance.
- Franklin Huang and team are investigating the genomic and molecular differences that may contribute to prostate cancer disparities in AA patients, and are deploying novel interventions to sustainably improve diversity and inclusion in genomic research.
- The team will identify genomic alterations among AA patients vs. EA patients with metastatic hormone sensitive prostate cancer (mHSPC) and castration-resistant prostate cancer (mCRPC) disease states.
- The team will develop and test an online tool that delivers health information and education on tumor genomic testing as a pre-test counseling tool, to improve recruitment of AA patients with metastatic prostate cancer to genomic research studies.
- The team will also develop and expand a high-impact, reproducible training program for underrepresented minority trainees in computational genomics and prostate cancer disparities.
- If successful, this project will identify unique tumor biology in AA patients that may lead to improved precision medicine treatment approaches, as well as improve recruitment of AA patients to prostate cancer clinical trials, and increase the numbers of underrepresented minority trainees in the computational prostate cancer disparities research field.
What this means to patients: African American (AA) patients experience significant disparities in prostate cancer diagnosis and outcomes compared with European American (EA) patients. Dr. Huang and team will map the landscape of genomic alterations in AA prostate cancers, which will enable new precision medicine approaches to be developed for AA patients. The team will also create a digital health tool that will increase ethnic and racial diversity in prostate cancer clinical trials, and develop a training program to increase the numbers of underrepresented minorities in the computational prostate cancer disparities research field.
2021 Movember-Distinguished Gentleman’s Ride-PCF Challenge Award
Principal Investigator: Matthew Freedman, MD (Harvard: Dana-Farber Cancer Institute)
Co-Investigators: Mark Pomerantz, MD (Dana-Farber Cancer Institute), Wilbert Zwart, PhD (The Netherlands Cancer Institute), Sylvan Baca, MD, PhD (Dana-Farber Cancer Institute), Tesa Severson, PhD (Netherlands Cancer Institute)
Project Title: Leveraging Epigenomics to Target Acquired Vulnerabilities in Treatment Resistant Prostate Cancer
- Epigenetics are chemical modifications on DNA that control which genes can and cannot be expressed, and enable the human body to have many different cell types using an identical genome. Alterations in epigenetic patterns play a major role in cancer.
- Dr. Freedman and team are investigating the role of epigenetic alterations in the development of resistance to anti-androgen therapy and progression to neuroendocrine prostate cancer (NEPC), a highly aggressive form of treatment-resistant prostate cancer.
- The team previously identified patterns of epigenetic changes in prostate cancer samples that tracked with development of metastasis, metastatic castration resistant prostate cancer (mCRPC) and NEPC. 35 master transcription regulators, including FOXA1, HOXB13, and ASCL1, were found to collectively regulate the genes affected by the epigenetic changes, suggesting they are major drivers of prostate cancer progression and may be promising therapeutic targets.
- In this project, the team will investigate whether targeting any of these transcription regulators in preclinical prostate cancer models will prevent the development of resistance to anti-androgen therapy and progression to NEPC.
- For 25 of the 35 transcriptional regulators, candidate small molecule inhibitors are available. These will be assessed for their efficacy and safety as potential prostate cancer treatments.
- The team will also create a metastatic prostate cancer epigenomic resource for the research community, to accelerate translational research on the development of treatment resistance and NEPC. This resource will be comprised of genomic, gene expression, and epigenetic data from patient samples across the advanced prostate cancer disease spectrum.
- If successful, this project will enable the identification of novel therapeutic targets and treatments to prevent progression to metastatic treatment resistant prostate cancer.
What this means to patients: Once prostate cancer has progressed to a metastatic treatment-resistant state, there are no curative treatment options yet discovered. Dr. Freedman and team have identified a set of transcriptional regulators that control the conversion of prostate cancer to metastatic and treatment-resistant states, and are testing whether these may serve as promising treatment targets. This will lead to new treatments that prevent development of advanced, lethal prostate cancer. The team is also developing a prostate cancer research resource, which will enable other researchers to more rapidly uncover novel biology and treatment opportunities for prostate cancer patients.