A5068667672- Prostate Cancer Treatment and Research
- Cancer Immunotherapy and Biomarkers
- Cancer, Lipids, and Metabolism
- Peptidase Inhibition and Analysis
- Immunotherapy and Immune Responses
- Prostate Cancer Diagnosis and Treatment
- Radiopharmaceutical Chemistry and Applications
- Cancer-related gene regulation
- Heat shock proteins research
- Protein Hydrolysis and Bioactive Peptides
- vaccines and immunoinformatics approaches
- RNA modifications and cancer
- Cancer-related molecular mechanisms research
- Wnt/β-catenin signaling in development and cancer
- Ubiquitin and proteasome pathways
- Ferroptosis and cancer prognosis
- Neuroendocrine Tumor Research Advances
- Bladder and Urothelial Cancer Treatments
- Hormonal and reproductive studies
- Cytokine Signaling Pathways and Interactions
- Genetic factors in colorectal cancer
- Drug Transport and Resistance Mechanisms
- Medical Imaging Techniques and Applications
- RNA Research and Splicing
- Quinazolinone synthesis and applications
Beth Israel Deaconess Medical Center
2017-2023
Harvard University
2017-2023
University of California, Los Angeles
2021
Patients with locally advanced prostate cancer have an increased risk of recurrence and mortality. In this phase II trial, we evaluate neoadjuvant enzalutamide leuprolide (EL) or without abiraterone prednisone (ELAP) before radical prostatectomy (RP) in men cancer.Eligible patients had a biopsy Gleason score 4 + 3 = 7 greater, prostate-specific antigen (PSA) greater than 20 ng/mL, T3 disease (by magnetic resonance imaging). Lymph nodes were required to be smaller mm. randomly assigned 2:1...
This multicenter randomized phase 2 trial investigates the impact of intense androgen deprivation on radical prostatectomy pathologic response and radiographic tissue biomarkers in localized prostate cancer (NCT02903368).Eligible patients had a Gleason score ≥4+3=7, specific antigen >20 ng/mL or T3 disease lymph nodes <20 mm. In Part 1, were 1:1 to apalutamide, abiraterone acetate, prednisone leuprolide (AAPL) abiraterone, prednisone, (APL) for 6 cycles (1 cycle=28 days) followed by...
Purpose: Programmed cell death ligand-1 (PD-L1)/programmed death-1 (PD-1) blockade has been unsuccessful in prostate cancer, with poor immunogenicity and subsequent low PD-L1 expression cancer being proposed as an explanation. However, recent studies indicate that a subset of may express significant levels PD-L1. Furthermore, the androgen antagonist enzalutamide shown to upregulate preclinical models. In this study, we evaluated effect neoadjuvant deprivation therapy abiraterone acetate plus...
Primary prostate cancer can have extensive microheterogeneity, but its contribution to the later emergence of metastatic castration-resistant (mCRPC) remains unclear. In this study, we microdissected residual foci in radical prostatectomies from 18 men treated with neoadjuvant-intensive androgen deprivation therapy (leuprolide, abiraterone acetate, and prednisone) analyzed them for resistance mechanisms. Transcriptome profiling showed reduced persistent receptor (AR) activity tumors, no...
The standard treatment for metastatic prostate cancer, androgen deprivation therapy (ADT), is designed to suppress receptor (AR) activity. However, men invariably progress castration-resistant cancer (CRPC), and AR reactivation contributes progression in most cases. To identify mechanisms that may drive CRPC, we examined a VCaP xenograft model as tumors progressed from initial sensitivity prior castration resistance then on relapse after combined with further AR-targeted drugs (abiraterone...
Despite widespread use of taxanes, mechanisms action and resistance in vivo remain to be established, there is no way predicting who will respond therapy. This study examined prostate cancer (PCa) xenografts patient samples identify taxane resistance. Docetaxel drug-target engagement was assessed by confocal anti-tubulin immunofluorescence quantify microtubule bundling interphase cells aberrant mitoses. Tumor biopsies from metastatic PCa patients obtained 2 5 days after their first dose...
Androgen receptor (AR) is the principal molecule in prostate cancer (PCa) etiology and therapy. AR re‐activation still remains a major challenge during treatment of castration‐resistant (CRPC) tumors that relapse after castration therapies. Recent reports have indicated enrichment Ser81‐phosphorylated (pS81) nucleus CRPC cells, CDK1 CDK9 as kinases phosphorylating at S81. In current study we showed pS81 preferentially localized both rapid biopsy metastatic samples PCa xenografts, nuclear...
Abstract Wnt signaling driven by genomic alterations in genes including APC and CTNNB, which encodes β-catenin, have been implicated prostate cancer development progression to metastatic castration-resistant (mCRPC). However, nongenomic drivers downstream effectors of the therapeutic potential targeting this pathway not fully established. Here we analyzed Wnt/β-catenin identified distinct from those found other tissues, aryl hydrocarbon receptor RUNX1, are linked stem cell maintenance, ROR1,...
Metastatic prostate cancer is initially sensitive to androgen receptor inhibition, but eventually becomes castration-resistant (mCRPC). Early use of more intensive therapies targeting and other oncogenic drivers in treatment-naïve primary (PC) may be effective than that advanced mCRPC. However, analysis tumors not reveal targetable metastatic are subclonal the tumor or acquired at sites.PC samples spanning one patient's clinical course: diagnostic biopsies, pre- post-enzalutamide rapid...
BACKGROUNDProstate cancer is multifocal with distinct molecular subtypes. The utility of genomic subtyping has been challenged due to inter- and intrafocal heterogeneity. We sought characterize the subtype-defining alterations primary prostate across all tumor foci within radical prostatectomy (RP) specimens determine prevalence collision tumors.METHODSFrom Early Detection Research Network cohort, we identified 333 prospectively collected RPs from 2010 2014 assessed ETS-related gene (ERG),...
// Kendra A. Williams 1 , Minnkyong Lee Jean M. Winter Derek E. Gildea 2 Carla Calagua 3 Natasha L. Curry Jens Lichtenberg Huihui Ye and Nigel P.S. Crawford 1, 4 Genetics Molecular Biology Branch, National Human Genome Research Institute, Institutes of Health, Bethesda, Maryland, USA Computational Statistical Genomics Department Pathology, Beth Israel Deaconess Medical Center, Harvard School, Boston, Massachusetts, Current address: Sanofi, Bridgewater, New Jersey, Correspondence to:...
Abstract Prostate cancers are considered immunologically ‘cold’ tumors given the very few patients who respond to checkpoint inhibitor therapy (CPI). Recently, enrichment of interferon (IFN) response genes predicts a favorable CPI across various disease sites. The enhancer zeste homolog-2 (EZH2) is over-expressed in prostate cancer and known negatively regulate IFN genes. Here, we demonstrate that inhibition EZH2 catalytic activity models derepresses expression double-strand RNA (dsRNA),...
<div>Abstract<p>Wnt signaling driven by genomic alterations in genes including <i>APC</i> and <i>CTNNB</i>, which encodes β-catenin, have been implicated prostate cancer development progression to metastatic castration-resistant (mCRPC). However, nongenomic drivers downstream effectors of Wnt the therapeutic potential targeting this pathway not fully established. Here we analyzed Wnt/β-catenin identified distinct from those found other tissues, aryl...
Supplementary Data from Autocrine Canonical Wnt Signaling Primes Noncanonical through ROR1 in Metastatic Castration-Resistant Prostate Cancer
TPS341 Background: Although androgen deprivation therapy (ADT) may be used for high-risk BCR PCa prior to radiographic metastases, evidence is lacking and toxicities are clear. Recent data show higher prevalence of programmed death-ligand 1 (PD-L1) expression in primary than previously seen. Tumor PD-L1 also significantly correlates with risk BCR, suggesting that inhibition innate immune function could associated recurrence. Finally, immune-suppressive cells increase after castration...
Abstract Purpose A subset of primary prostate cancer (PCa) expresses programmed death-ligand 1 (PD-L1), but whether they have unique tumor immune microenvironment (TIME) or genomic features is unclear. Experimental Design We selected PD-L1-positive high-grade and/or high-risk PCa, characterized tumor-infiltrating lymphocytes (TILS) with multiplex immunofluorescence, and identified alterations in immunogenic non-immunogenic foci. Results One-quarter aggressive localized PCa cases (29/115) had...
<div>AbstractPurpose:<p>A subset of primary prostate cancer expresses programmed death-ligand 1 (PD-L1), but whether they have a unique tumor immune microenvironment or genomic features is unclear.</p>Experimental Design:<p>We selected PD-L1–positive high-grade and/or high-risk cancer, characterized tumor-infiltrating lymphocytes with multiplex immunofluorescence, and identified alterations in immunogenic nonimmunogenic foci.</p>Results:<p>One quarter...
Supplementary Data from A Subset of Localized Prostate Cancer Displays an Immunogenic Phenotype Associated with Losses Key Tumor Suppressor Genes
Supplementary Data from A Subset of Localized Prostate Cancer Displays an Immunogenic Phenotype Associated with Losses Key Tumor Suppressor Genes
<div>AbstractPurpose:<p>A subset of primary prostate cancer expresses programmed death-ligand 1 (PD-L1), but whether they have a unique tumor immune microenvironment or genomic features is unclear.</p>Experimental Design:<p>We selected PD-L1–positive high-grade and/or high-risk cancer, characterized tumor-infiltrating lymphocytes with multiplex immunofluorescence, and identified alterations in immunogenic nonimmunogenic foci.</p>Results:<p>One quarter...
Supplementary Data from A Subset of Localized Prostate Cancer Displays an Immunogenic Phenotype Associated with Losses Key Tumor Suppressor Genes