Disrupting prostate cancer research: Challenge accepted; report from the 2023 Coffey-Holden Prostate Cancer Academy Meeting.

INTRODUCTION: The 2023 Coffey-Holden Prostate Cancer Academy (CHPCA) Meeting, themed "Disrupting Prostate Cancer Research: Challenge Accepted," was convened at the University of California, Los Angeles, Luskin Conference Center, in Los Angeles, CA, from June 22 to 25, 2023. METHODS: The 2023 marked the 10th Annual CHPCA Meeting, a discussion-oriented scientific think-tank conference convened annually by the Prostate Cancer Foundation, which centers on innovative and emerging research topics deemed pivotal for advancing critical unmet needs in prostate cancer research and clinical care. The 2023 CHPCA Meeting was attended by 81 academic investigators and included 40 talks across 8 sessions. RESULTS: The central topic areas covered at the meeting included: targeting transcription factor neo-enhancesomes in cancer, AR as a pro-differentiation and oncogenic transcription factor, why few are cured with androgen deprivation therapy and how to change dogma to cure metastatic prostate cancer without castration, reducing prostate cancer morbidity and mortality with genetics, opportunities for radiation to enhance therapeutic benefit in oligometastatic prostate cancer, novel immunotherapeutic approaches, and the new era of artificial intelligence-driven precision medicine. DISCUSSION: This article provides an overview of the scientific presentations delivered at the 2023 CHPCA Meeting, such that this knowledge can help in facilitating the advancement of prostate cancer research worldwide.

The 29th Annual Prostate Cancer Foundation Scientific Retreat Report.

BACKGROUND: The 29th Annual Prostate Cancer Foundation (PCF) Scientific Retreat was held from October 27 to 29, 2022, at the Omni La Costa Resort in Carlsbad, CA. This was the first-ever hybrid PCF Retreat. METHODS: The Annual PCF Scientific Retreat is a prominent international scientific gathering centered on groundbreaking, unpublished, and influential studies in basic, translational, and clinical prostate cancer research. It also covers research from related fields with a strong potential for influencing prostate cancer research and patient care. RESULTS: Key areas of research that were focused on at the 2022 PCF Retreat included: (i) the contributions of molecular and genomic factors to prostate cancer disparities; (ii) novel clinical trial updates; (iii) lessons from primary prostate cancer; (iv) lessons from single-cell studies; (v) genetic, epigenetic, epitranscriptomic and posttranslational mechanisms and clinical heterogeneity in prostate cancer; (vi) biology of neuroendocrine and lineage-plastic prostate cancer; (vii) next generation prostate cancer theranostics and combination therapies; (viii) the biology and therapeutic potential of targeting phosphoinositide 3-kinases pathways; (ix) combining immunomodulatory treatments for prostate cancer; (x) novel gamma delta (γδ) T-cell therapy platforms for oncology; and (xi) lessons from other cancers. CONCLUSIONS: This article provides a summary of the presentations from the 2022 PCF Scientific Retreat. By disseminating this knowledge, we hope to enhance our understanding of the present research landscape and guide future strides in both prostate cancer research and patient care.

Expression and Therapeutic Targeting of TROP-2 in Treatment-Resistant Prostate Cancer.

PURPOSE: Men with metastatic castration-resistant prostate cancer (mCRPC) frequently develop resistance to androgen receptor signaling inhibitor (ARSI) treatment; therefore, new therapies are needed. Trophoblastic cell-surface antigen (TROP-2) is a transmembrane protein identified in prostate cancer and overexpressed in multiple malignancies. TROP-2 is a therapeutic target for antibody-drug conjugates (ADC). EXPERIMENTAL DESIGN: TROP-2 gene (TACSTD2) expression and markers of treatment resistance from prostate biopsies were analyzed using data from four previously curated cohorts of mCRPC (n = 634) and the PROMOTE study (dbGaP accession phs001141.v1.p1, n = 88). EPCAM or TROP-2-positive circulating tumor cells (CTC) were captured from peripheral blood for comparison of protein (n = 15) and gene expression signatures of treatment resistance (n = 40). We assessed the efficacy of TROP-2-targeting agents in a mouse xenograft model generated from prostate cancer cell lines. RESULTS: We demonstrated that TACSTD2 is expressed in mCRPC from luminal and basal tumors but at lower levels in patients with neuroendocrine prostate cancer. Patients previously treated with ARSI showed no significant difference in TACSTD2 expression, whereas patients with detectable AR-V7 expression showed increased expression. We observed that TROP-2 can serve as a cell surface target for isolating CTCs, which may serve as a predictive biomarker for ADCs. We also demonstrated that prostate cancer cell line xenografts can be targeted specifically by labeled anti-TROP-2 agents in vivo. CONCLUSIONS: These results support further studies on TROP-2 as a therapeutic and diagnostic target for mCRPC.

Exploring new frontiers in prostate cancer research: Report from the 2022 Coffey-Holden prostate cancer academy meeting.

INTRODUCTION: The 2022 Coffey-Holden Prostate Cancer Academy (CHPCA) Meeting, "Exploring New Frontiers in Prostate Cancer Research," was held from June 23 to 26, 2022, at the University of California, Los Angeles, Luskin Conference Center, in Los Angeles, CA. METHODS: The CHPCA Meeting is an annual discussion-oriented scientific conference organized by the Prostate Cancer Foundation, that focuses on emerging and next-step topics deemed critical for making the next major advances in prostate cancer research and clinical care. The 2022 CHPCA Meeting included 35 talks over 10 sessions and was attended by 73 academic investigators. RESULTS: Major topic areas discussed at the meeting included: prostate cancer diversity and disparities, the impact of social determinants on research and patient outcomes, leveraging real-world and retrospective data, development of artificial intelligence biomarkers, androgen receptor (AR) signaling biology and new strategies for targeting AR, features of homologous recombination deficient prostate cancer, and future directions in immunotherapy and nuclear theranostics. DISCUSSION: This article summarizes the scientific presentations from the 2022 CHPCA Meeting, with the goal that dissemination of this knowledge will contribute to furthering global prostate cancer research efforts.

The 28th Annual Prostate Cancer Foundation Scientific Retreat report.

BACKGROUND: The 28th Annual Prostate Cancer Foundation (PCF) Scientific Retreat was held virtually over 4 days, on October 28-29 and November 4-5, 2021. METHODS: The Annual PCF Scientific Retreat is a leading global scientific conference that focuses on first-in-field, unpublished, and high-impact basic, translational, and clinical prostate cancer research, as well as research from other fields with high probability for impacting prostate cancer research and patient care. RESULTS: Primary areas of research discussed at the 2021 PCF Retreat included: (i) prostate cancer disparities; (ii) prostate cancer survivorship; (iii) next-generation precision medicine; (iv) PSMA theranostics; (v) prostate cancer lineage plasticity; (vi) tumor metabolism as a cancer driver and treatment target; (vii) prostate cancer genetics and polygenic risk scores; (viii) glucocorticoid receptor biology in castration-resistant prostate cancer (CRPC); (ix) therapeutic degraders; (x) new approaches for immunotherapy in prostate cancer; (xi) novel technologies to overcome the suppressive tumor microenvironment; and (xii) real-world evidence and synthetic/virtual control arms. CONCLUSIONS: This article provides a summary of the presentations from the 2021 PCF Scientific Retreat. We hope that sharing this knowledge will help to improve the understanding of the current state of research and direct new advances in prostate cancer research and care.

Prostate cancer research in the 21st century; report from the 2021 Coffey-Holden prostate cancer academy meeting.

INTRODUCTION: The 2021 Coffey-Holden Prostate Cancer Academy (CHPCA) Meeting, "Prostate Cancer Research in the 21st Century," was held virtually, from June 24-25, 2021. METHODS: The CHPCA Meeting is organized by the Prostate Cancer Foundation as a unique discussion-oriented meeting focusing on critical topics in prostate cancer research envisioned to bridge the next major advances in prostate cancer biology and treatment. The 2021 CHPCA Meeting was virtually attended by 89 investigators and included 31 talks over nine sessions. RESULTS: Major topic areas discussed at the meeting included: cancer genomics and sequencing, functional genomic approaches to studying mediators of plasticity, emerging signaling pathways in metastatic castration resistant prostate cancer, Wnt signaling biology and the challenges of targeted therapy, clonal hematopoiesis, neuroendocrine cell plasticity and antitumor immunity, cancer immunotherapy and its synergizers, and imaging the tumor microenvironment and metabolism. DISCUSSION: This meeting report summarizes the research presented at the 2021 CHPCA Meeting. We hope that publication of this knowledge will accelerate new understandings and the development of new biomarkers and treatments for prostate cancer.

The History of Prostate-Specific Membrane Antigen as a Theranostic Target in Prostate Cancer: The Cornerstone Role of the Prostate Cancer Foundation.

Prostate-specific membrane antigen (PSMA) is a credentialed imaging and therapy (theranostic) target for the detection and treatment of prostate cancer. PSMA-targeted PET imaging and molecular radiotherapy are promising evolving technologies that will improve the outcomes of prostate cancer patients. In anticipation of this new era in prostate cancer theranostics, this article will review the history of PSMA from discovery through early- and late-stage clinical trials. Since 1993, the Prostate Cancer Foundation has funded critical and foundational PSMA research that established this theranostic revolution. The history and role of Prostate Cancer Foundation funding in this field will be discussed.

Prostate Cancer Racial Disparities: A Systematic Review by the Prostate Cancer Foundation Panel.

CONTEXT: Prostate cancer (PCa) is a complex disease that disproportionately impacts Black men in the USA. The structural factors that drive heterogeneous outcomes for patients of differing backgrounds are probably the same ones that result in population-level disparities. The relative contribution of drivers along the PCa disease continuum is an active area of investigation and debate. OBJECTIVE: To critically synthesize the available evidence on PCa disparities from a population-level perspective in comparison to data from "equal access and equal care settings" and to provide a consensus summary of the state of PCa disparities. EVIDENCE ACQUISITION: A plenary panel on PCa disparities presented at the Prostate Cancer Foundation meeting on October 24, 2019 and ensuing discussions are reported here. We used a systematic literature review approach and the Preferred Reporting Items for Systematic Reviews and Meta-analyses to select the most relevant publications. A total of 3333 publications between 2011 and 2021 were retrieved, of which 52 were included in the review; an additional 13 articles on screening guidelines, seminal clinical trials, and statistical methodology were used in the evidence synthesis. EVIDENCE SYNTHESIS: Race disparities in PCa are a result of a complex interaction between socioeconomic factors impacting access to care and ancestral/genetic factors that may influence tumor biology. Black men in the USA continue to have a nearly 1.8 times higher population-level incidence rate than White men. Failure to account for the race-specific incidence burden would continue to lead to residual disparity even after achieving relatively similar outcomes after primary treatment, resulting in a higher long-term mortality burden. Selection bias remains possible in PCa studies, which often rely on highly specific cohorts of Black men with higher use of health care resources that may not represent the average Black patient in the USA. Novel methods including mediation analysis and genetic ancestry rather than self-identified race can optimize analytical models investigating racial disparities and may lead to a better understanding of PCa genomic diversity and behavior. CONCLUSIONS: Our findings emphasize the importance of racially diverse studies, including precision -omics, prevention, and targeted therapy initiatives, to elucidate mechanisms underlying racial differences in outcomes and response to therapy. We propose novel approaches for studying and addressing PCa disparities. Contemporary methods, particularly in the domain of mediation analysis, can promote scientific rigor in understanding these disparities. PATIENT SUMMARY: Inaccurate data interpretation or lack of data altogether for Black men can impact policy and ultimately affect millions of individuals of African origin worldwide. Our review identifies a need to develop and prioritize a strategy for including Black and other men with prostate cancer in intervention studies and randomized clinical trials to halt the widening prostate cancer disparities.

The 27th Annual Prostate Cancer Foundation Scientific Retreat Report.

BACKGROUND: The 27th Annual Prostate Cancer Foundation (PCF) Scientific Retreat was held virtually from October 20 to 23, 2020. METHODS: The Annual PCF Scientific Retreat is a global scientific research conference that highlights the most promising and cutting edge advances in prostate cancer basic, translational and clinical research, as well as research from other fields with a strong potential for advancing prostate cancer research. RESULTS: Primary areas of research discussed at the 2020 PCF Retreat included: (i) the intersection between prostate cancer and COVID-19 research; (ii) lessons from the COVID-19 pandemic that may address prostate cancer disparities; (iv) the role of the microbiome in cancer; (v) current challenges in treatment of patients with metastatic prostate cancer; (viii) prostate cancer germline genetics and evolutionary genomics; (ix) advances in circulating DNA methylation biomarkers for diagnosis, prognosis, and treatment selection; (x) advances in the development of MYC-targeting therapeutics; (xi) advances in antibody-drug conjugates for the treatment of cancer; (xii) advances for immunotherapy in prostate cancer; and (xiii) updates from other recent prostate cancer clinical trials. CONCLUSIONS: This article summarizes the research presented at the 2020 PCF Scientific Retreat. We hope that dissemination of this knowledge will help to accelerate and direct the next major advances in prostate cancer research and care.

The 26th Annual Prostate Cancer Foundation Scientific Retreat Report.

BACKGROUND: The 26th Annual Prostate Cancer Foundation (PCF) Scientific Retreat was held from October 24-26, 2019 in Carlsbad, CA. METHODS: The Annual PCF Scientific Retreat is a global scientific research conference that focuses on the most promising and interesting new research in the prostate cancer field, and topics arising from other fields that have the potential to impact and advance prostate cancer research and clinical care. RESULTS: The primary topic areas addressed at the 2019 PCF Retreat included: (i) new insights into prostate cancer biology and treatment; (ii) new drugs and drug targets in prostate cancer; (iii) advances in prostate cancer genomics; (iv) lessons from the multi-arm, multistage randomized phase 3 STAMPEDE trial; (v) advances in immunotherapy for prostate cancer; (vi) factors contributing to prostate cancer racial disparities; (vii) treatment-associated small-cell/neuroendocrine prostate cancer (t-SCNC); (viii) artificial intelligence and machine learning in cancer research and development; (ix) population science research on prostate cancer; and (x) prostate cancer research in the Department of Veterans Affairs. CONCLUSIONS: This article reviews the presentations from the 2019 PCF Scientific Retreat. We hope that this knowledge will accelerate research leading to new understandings of prostate cancer biology and improve treatments for patients with prostate cancer.

Prostate Cancer Foundation Hormone-Sensitive Prostate Cancer Biomarker Working Group Meeting Summary.

Androgen deprivation therapy remains the backbone therapy for the treatment of metastatic hormone-sensitive prostate cancer (mHSPC). In recent years, several treatments, including docetaxel, abiraterone + prednisone, enzalutamide, and apalutamide, have each been shown to demonstrate survival benefit when used upfront along with androgen deprivation therapy. However, treatment selection for an individual patient remains a challenge. There is no high level clinical evidence for treatment selection among these choices based on biological drivers of clinical disease. In August 2020, the Prostate Cancer Foundation convened a working group to meet and discuss biomarkers for hormone-sensitive prostate cancer, the proceedings of which are summarized here. This meeting covered the state of clinical and biological evidence for systemic therapies in the mHSPC space, with emphasis on charting a course for the generation, interrogation, and clinical implementation of biomarkers for treatment selection.

Prostate Cancer Foundation-Department of Veterans Affairs Partnership: A Model of Public-Private Collaboration to Advance Treatment and Care of Invasive Cancers.

BACKGROUND: Prostate cancer is the most frequently diagnosed and treated cancer in the US Department of Veterans Affairs (VA). As the leading philanthropic source for prostate cancer research, the Prostate Cancer Foundation (PCF) entered into a unique public-private biomedical research partnership with the VA with the goal of addressing the urgent health challenges faced by veterans with prostate cancer. OBSERVATIONS: With a commitment of $50 million from PCF and the VA's vast medical center infrastructure, the PCF-VA partnership has established 12 precision oncology Centers of Excellence to date, forming a collaborative network called the Precision Oncology Program for Cancer of the Prostate (POPCaP) Network. A 4-year review reveals the importance of executive leadership, mission-driven advocacy, setting shared ambitious goals, maximizing existing infrastructure and human capital, recruiting talent and resources, and creating space for adaptation and iteration in the context of a learning health care system. CONCLUSIONS: The PCF-VA partnership seeks to continue translating clinical research into national standards of care for veterans and serves as an innovative model of public-private collaborations for future health initiatives.

Meeting report from the Prostate Cancer Foundation PSMA theranostics state of the science meeting.

INTRODUCTION: The Prostate Cancer Foundation (PCF) convened a PCF prostate-specific membrane antigen (PSMA) Theranostics State of the Science Meeting on 18 November 2019, at Weill Cornell Medicine, New York, NY. METHODS: The meeting was attended by 22 basic, translational, and clinical researchers from around the globe, with expertise in PSMA biology, development and use of PSMA theranostics agents, and clinical trials. The goal of this meeting was to discuss the current state of knowledge, the most important biological and clinical questions, and critical next steps for the clinical development of PSMA positron emission tomography (PET) imaging agents and PSMA-targeted radionuclide agents for patients with prostate cancer. RESULTS: Several major topic areas were discussed including the biology of PSMA, the role of PSMA-targeted PET imaging in prostate cancer, the physics and performance of different PSMA-targeted PET imaging agents, the current state of clinical development of PSMA-targeted radionuclide therapy (RNT) agents, the role of dosimetry in PSMA RNT treatment planning, barriers and challenges in PSMA RNT clinical development, optimization of patient selection for PSMA RNT trials, and promising combination treatment approaches with PSMA RNT. DISCUSSION: This article summarizes the presentations from the meeting for the purpose of globally disseminating this knowledge to advance the use of PSMA-targeted theranostic agents for imaging and treatment of patients with prostate cancer.

Implementation of Germline Testing for Prostate Cancer: Philadelphia Prostate Cancer Consensus Conference 2019.

PURPOSE: Germline testing (GT) is a central feature of prostate cancer (PCA) treatment, management, and hereditary cancer assessment. Critical needs include optimized multigene testing strategies that incorporate evolving genetic data, consistency in GT indications and management, and alternate genetic evaluation models that address the rising demand for genetic services. METHODS: A multidisciplinary consensus conference that included experts, stakeholders, and national organization leaders was convened in response to current practice challenges and to develop a genetic implementation framework. Evidence review informed questions using the modified Delphi model. The final framework included criteria with strong (> 75%) agreement (Recommend) or moderate (50% to 74%) agreement (Consider). RESULTS: Large germline panels and somatic testing were recommended for metastatic PCA. Reflex testing-initial testing of priority genes followed by expanded testing-was suggested for multiple scenarios. Metastatic disease or family history suggestive of hereditary PCA was recommended for GT. Additional family history and pathologic criteria garnered moderate consensus. Priority genes to test for metastatic disease treatment included BRCA2, BRCA1, and mismatch repair genes, with broader testing, such as ATM, for clinical trial eligibility. BRCA2 was recommended for active surveillance discussions. Screening starting at age 40 years or 10 years before the youngest PCA diagnosis in a family was recommended for BRCA2 carriers, with consideration in HOXB13, BRCA1, ATM, and mismatch repair carriers. Collaborative (point-of-care) evaluation models between health care and genetic providers was endorsed to address the genetic counseling shortage. The genetic evaluation framework included optimal pretest informed consent, post-test discussion, cascade testing, and technology-based approaches. CONCLUSION: This multidisciplinary, consensus-driven PCA genetic implementation framework provides novel guidance to clinicians and patients tailored to the precision era. Multiple research, education, and policy needs remain of importance.

Accelerating precision medicine in metastatic prostate cancer.

Despite advances in prostate cancer screening and treatment, available therapy options, particularly in later stages of the disease, remain limited and the treatment-resistant setting represents a serious unmet medical need. Moreover, disease heterogeneity and disparities in patient access to medical advances result in significant variability in outcomes across patients. Disease classification based on genomic sequencing is a promising approach to identify patients whose tumors exhibit actionable targets and make more informed treatment decisions. Here we discuss how we can accelerate precision oncology to inform broader genomically-driven clinical decisions for men with advanced prostate cancer, drug development and ultimately contribute to new treatment paradigms.

Prostate cancer research: The next generation; report from the 2019 Coffey-Holden Prostate Cancer Academy Meeting.

INTRODUCTION: The 2019 Coffey-Holden Prostate Cancer Academy (CHPCA) Meeting, "Prostate Cancer Research: The Next Generation," was held 20 to 23 June, 2019, in Los Angeles, California. METHODS: The CHPCA Meeting is an annual conference held by the Prostate Cancer Foundation, that is uniquely structured to stimulate intense discussion surrounding topics most critical to accelerating prostate cancer research and the discovery of new life-extending treatments for patients. The 7th Annual CHPCA Meeting was attended by 86 investigators and concentrated on many of the most promising new treatment opportunities and next-generation research technologies. RESULTS: The topics of focus at the meeting included: new treatment strategies and novel agents for targeted therapies and precision medicine, new treatment strategies that may synergize with checkpoint immunotherapy, next-generation technologies that visualize tumor microenvironment (TME) and molecular pathology in situ, multi-omics and tumor heterogeneity using single cells, 3D and TME models, and the role of extracellular vesicles in cancer and their potential as biomarkers. DISCUSSION: This meeting report provides a comprehensive summary of the talks and discussions held at the 2019 CHPCA Meeting, for the purpose of globally disseminating this knowledge and ultimately accelerating new treatments and diagnostics for patients with prostate cancer.

Advances in germline genetics for prostate cancer funded by the Prostate Cancer Foundation.

The Prostate Cancer Foundation (PCF) is the world's largest non-profit organization that funds patient-centric prostate cancer research. PCF has funded numerous critical studies surrounding the identification, biology, and clinical significance of prostate cancer germline and somatic genetic alterations, and is accelerating the application of these findings to improving outcomes for patients and their families.

The 25th Annual Prostate Cancer Foundation Scientific Retreat Report.

BACKGROUND: The 25th Annual Prostate Cancer Foundation (PCF) Scientific Retreat was held in Carlsbad, CA, from 26 to 28 October 2018. METHODS: The PCF Scientific Retreat is the foremost scientific research conference in the world that focuses on the most significant and promising recent advancements in basic, translational, and clinical prostate cancer research, as well as research from other fields that has substantial potential to advance prostate cancer research. RESULTS: The major topic areas discussed at this year's meeting included (a) new insights into prostate cancer biology and treatment; (b) approaches for accelerating precision medicine for prostate cancer; (c) prostate-specific membrane antigen-targeted therapy and imaging for prostate cancer; (d) updates on Poly (ADP-ribose) polymerase (PARP)-inhibitor clinical trial results; (e) the biology and role of prostate cancer stem cells; (f) new approaches for targeting the androgen receptor and other steroid hormone receptor pathways; (g) racial disparities in prostate cancer treatment and outcomes; (h) the role of the nervous system in prostate cancer development and progression; (i) the role of the WNT signaling pathway in normal prostate and prostate cancer biology; (j) novel immunotherapy approaches; and (k) the ecology of prostate cancer. CONCLUSIONS: This article reviews the research presented by the speakers at the 2018 PCF Scientific Retreat for the purpose of disseminating this knowledge to the global research community and ultimately accelerating new understandings and treatment strategies for prostate cancer.