Project Grant R01CA287669

Award Date 7/1/24
Completion Date 6/30/29
Dollars Obligated $1.1M
Federal Grant Program
93.395
Assistance Type
Project Grant
Place of Performance
Los Angeles, CA 90095, USA
Similar Awards
This Project Grant award from the National Cancer Institute (CFDA 93.394 - Cancer Detection and Diagnosis Research) provides $627,474 to the Dana-Farber Cancer Institute to conduct research aimed at leveraging innovative epigenomic methods and signatures to inform the understanding of prostate cancer lineage plasticity, including treatment-emergent neuroendocrine prostate cancer (NEPC). The key goals are to utilize epigenomic signatures to detect NEPC and predict enzalutamide resistance, as well...
This Project Grant award from the National Cancer Institute's Cancer Detection and Diagnosis Research program (CFDA 93.394) provides $680,453 to the University of Wisconsin System to develop a liquid biopsy approach using circulating tumor DNA (ctDNA) fragments and machine learning to monitor for the transition between prostate adenocarcinoma and neuroendocrine prostate cancer (NEPC) in metastatic castration-resistant prostate cancer (mCRPC) patients. The key objectives are to: 1) determine if...
This $832,818 Project Grant, awarded on December 5, 2024 by the National Cancer Institute (NCI) under the Cancer Cause and Prevention Research (CFDA 93.393) program, supports research by the University of Massachusetts Boston (UMass Boston) to investigate the role of the SETD7 enzyme in preventing prostate cancer progression and therapy resistance. The key objectives are to: 1) assess SETD7 protein expression and its correlation with LSD1, AR, and other epigenetic regulators in...
This National Cancer Institute project grant of $808,336 provides funding from September 2022 through August 2025 to investigate the effects of androgen receptor antagonism on human T cell function. The University of Portland will determine how androgen deprivation therapies used in prostate cancer treatment impact the adaptive immune response. Researchers will study the impact of the clinically relevant androgen receptor antagonist enzalutamide on T cells isolated from healthy volunteers in...
This Project Grant award of $371,719 from the National Cancer Institute (CFDA 93.393 - Cancer Cause and Prevention Research) supports research by the University of Pennsylvania to characterize epigenetic targets in prostate cancer. The key objectives are to: Gain mechanistic insights into how the histone methyltransferase NSD2 influences the chromatin landscape to facilitate the assembly of the androgen receptor (AR) enhanceosome complex and enhance AR-driven transcription in prostate cancer...
This federal Project Grant award for $710,980.00 from the National Cancer Institute (NCI) under the Cancer Treatment Research program (CFDA 93.395) supports research aimed at defining the molecular mechanisms and therapeutic potential of targeting the SPOP ubiquitin signaling pathway in prostate cancer. Key objectives include: Elucidating the role of the SPOP pathway regulator G3BP1 in driving prostate tumorigenesis and evaluating the ability to target this upstream axis. Establishing the...
The National Cancer Institute (NCI) awarded a $185,760 Project Grant under the Cancer Research Manpower (CFDA 93.398) program to The Regents of the University of California, San Francisco (UCSF) to develop a novel tumor-targeted combination therapy for metastatic castration-resistant prostate cancer (mCRPC). The project aims to enhance efficacy and reduce toxicity by co-delivering cytotoxic drugs and the radioactive isotope Actinium-225 directly to cancer cells. Key objectives include developing...
The National Cancer Institute (NCI) awarded a $1,948,592 Project Grant under the Cancer Treatment Research program (CFDA 93.395) to Washington University to conduct a Phase 1 clinical trial assessing the safety, tolerability, pharmacokinetics, and anti-tumor activity of the novel ACK1 inhibitor (R)-9B in patients with castration-resistant prostate cancer (CRPC). The grant period runs from August 15, 2024 to July 31, 2029. The study aims to evaluate (R)-9B's ability to overcome CRPC resistance...
This federal Project Grant award from the National Cancer Institute (CFDA 93.395 - Cancer Treatment Research) to The University of Texas Southwestern Medical Center provides $472,458 to conduct research aimed at overcoming mechanisms of PTPN1 driving therapy- and castration-resistant prostate cancer. The 5-year project, starting December 1, 2024, will investigate the regulation of the PTPN1 gene and its role in the transition of prostate cancer cells to a therapy-resistant neuroendocrine...
This Project Grant award from the National Cancer Institute (CFDA 93.393 - Cancer Cause and Prevention Research) will support research at Weill Medical College of Cornell University to investigate the role of the androgen receptor (AR) in both normal prostate cell function and prostate cancer development. The $564,543 award, effective March 1, 2025 through February 28, 2030, will enable the research team to determine the factors that mediate the switch between AR's normal, growth-suppressive...

TESTING ATAD2 AS A NEW THERAPEUTIC TARGET FOR ADVANCED PROSTATE CANCER - PROJECT SUMMARY/ABSTRACT PROSTATE CANCER IS THE SECOND LEADING CAUSE OF MALE CANCER DEATH. ADVANCED PROSTATE CANCER, WHETHER PRESENT AT THE TIME OF DIAGNOSIS OR ARISING AFTER TREATMENT OF LOCALIZED DISEASE, RESPONDS TO ANDROGEN DEPRIVATION, BUT INVARIABLY FAILS AND RECURS AS CASTRATION-RESISTANT PROSTATE CANCER (CRPC) WHICH IS THE MAIN CAUSE OF PROSTATE CANCER-ASSOCIATED MORTALITY. HEAVILY TREATED TUMORS, PARTICULARLY THOSE TREATED WITH SECONDARY HORMONE THERAPIES, FREQUENTLY ACQUIRE A NEUROENDOCRINE PHENOTYPE (NEPC), WHICH CURRENTLY ACCOUNTS FOR 15-20% OF CRPC. NEPC IS COMMONLY CHARACTERIZED BY EXPRESSION OF NEUROENDOCRINE MARKERS, AN AGGRESSIVE CLINICAL COURSE, AND DOWNREGULATION OR LOSS OF ANDROGEN RECEPTOR (AR) THAT DIMINISHES RESPONSIVENESS TO ANDROGEN DEPRIVATION THERAPIES, MAKING IT THE MOST LETHAL AND CURRENTLY INCURABLE SUBSET OF PROSTATE CANCER. THUS, THERE IS AN URGENT UNMET NEED TO DEFINE NEW THERAPEUTIC STRATEGIES FOR ADENO-CRPC AND NEPC. OUR RECENT STUDIES IDENTIFIED ATAD2 AS AN UP-REGULATED DRUGGABLE PROTEIN IN TREATMENT-INDUCED NEPC. MOREOVER, WE DEMONSTRATED THAT ATAD2 INHIBITORS DRAMATICALLY SUPPRESS NEPC CELL AND TUMOR GROWTH. THE GOALS OF THE STUDY ARE TO TEST THE THERAPEUTIC POTENTIAL OF ATAD2 INHIBITOR ALONE OR IN COMBINATION THERAPY SETTINGS IN PRE-CLINICAL MODELS OF ADENO-CRPC AND NEPC AND DEFINE NEW MECHANISMS THROUGH WHICH ATAD2 REGULATES PROSTATE TUMORIGENESIS. THE GOAL OF THIS PROPOSAL IS BASED ON STRONG PRELIMINARY RESULTS. WE PROPOSE TO USE CELL LINE MODELS OF ADENO-CRPC AND NEPC AS WELL AS PATIENT-DERIVED XENOGRAFTS (PDXS) OF ADENO-CRPC AND NEPC TO TEST THE PROPOSED COMBINATION THERAPIES IN PRE-CLINICAL SETTINGS. THE AIMS OF THE PROPOSED PROJECT ARE: SPECIFIC AIM 1. TEST THE LEVELS OF ATAD2 IN A LARGE COHORT OF CLINICAL SPECIMENS. SPECIFIC AIM 2. INVESTIGATE THE FUNCTIONAL ROLE OF ATAD2 IN ADVANCED PROSTATE CANCER AND DEFINE THE MOLECULAR MECHANISMS THROUGH WHICH ATAD2 CONTRIBUTES TO PROSTATE TUMORIGENESIS AND NEPC. SPECIFIC AIM 3. TEST THE THERAPEUTIC POTENTIAL OF ATAD2 INHIBITORS ALONE AND IN COMBINATION WITH THERAPIES USED AS A STANDARD OF CARE FOR PROSTATE CANCER IN ADENO-CRPC AND NEPC GROWTH AND METASTASIS.

Posted 6/28/24, 12:00 AM