A5054590690- Prostate Cancer Treatment and Research
- Hormonal and reproductive studies
- Cancer Genomics and Diagnostics
- Cancer, Lipids, and Metabolism
- Prostate Cancer Diagnosis and Treatment
- Bladder and Urothelial Cancer Treatments
- Estrogen and related hormone effects
- Radiopharmaceutical Chemistry and Applications
- PARP inhibition in cancer therapy
- Cancer Immunotherapy and Biomarkers
- Urinary and Genital Oncology Studies
- Genetic factors in colorectal cancer
- Peptidase Inhibition and Analysis
- Cell Adhesion Molecules Research
- Cancer Diagnosis and Treatment
- Epigenetics and DNA Methylation
- Ubiquitin and proteasome pathways
- Cancer Cells and Metastasis
- Cancer-related Molecular Pathways
- S100 Proteins and Annexins
- Radiomics and Machine Learning in Medical Imaging
- Bone health and treatments
- Multiple and Secondary Primary Cancers
- Cancer-related gene regulation
- Sexual Differentiation and Disorders
University of Washington
2016-2025
Fred Hutch Cancer Center
2015-2025
VA Puget Sound Health Care System
2011-2025
University of Puget Sound
2019-2025
University of Washington Medical Center
2005-2024
Seattle Cancer Care Alliance
2011-2023
National Institute of Standards and Technology
2023
Athira Pharma (United States)
2023
Seattle University
2010-2023
Prostate Cancer Foundation
2021-2023
A method for enumerating circulating tumor cells (CTC) has received regulatory clearance. The primary objective of this prospective study was to establish the relationship between posttreatment CTC count and overall survival (OS) in castration-resistant prostate cancer (CRPC). Secondary objectives included determining prognostic utility measurement before initiating therapy, prostate-specific antigen (PSA) changes OS at these other time points.Blood drawn from CRPC patients with progressive...
Inherited mutations in DNA-repair genes such as BRCA2 are associated with increased risks of lethal prostate cancer. Although the prevalence germline among men localized cancer who unselected for family predisposition is insufficient to warrant routine testing, frequency patients metastatic has not been established.
Abstract Therapy for advanced prostate cancer centers on suppressing systemic androgens and blocking activation of the androgen receptor (AR). Despite anorchid serum levels, nearly all patients develop castration-resistant disease. We hypothesized that ongoing steroidogenesis within tumors maintenance intratumoral may contribute to growth. Using mass spectrometry quantitative reverse transcription–PCR, we evaluated levels transcripts encoding steroidogenic enzymes in benign tissue, untreated...
Heterogeneity in the genomic landscape of metastatic prostate cancer has become apparent through several comprehensive profiling efforts, but little is known about impact this heterogeneity on clinical outcome. Here, we report and transcriptomic analysis 429 patients with castration-resistant (mCRPC) linked longitudinal outcomes, integrating findings from whole-exome, transcriptome, histologic analysis. For 128 treated a first-line next-generation androgen receptor signaling inhibitor (ARSI;...
Abiraterone is a potent inhibitor of the steroidogenic enzyme CYP17A1 and suppresses tumor growth in patients with castration-resistant prostate cancer (CRPC). The effectiveness abiraterone reducing androgens not known, nor have mechanisms contributing to resistance been established.We treated human CRPC xenografts measured growth, tissue androgens, androgen receptor (AR) levels, gene expression versus controls.Abiraterone suppressed serum PSA levels improved survival two distinct...
Abstract TMPRSS2 is an androgen-regulated cell-surface serine protease expressed predominantly in prostate epithelium. highly localized high-grade cancers and the majority of human cancer metastases. Through generation mouse models with a targeted deletion Tmprss2, we demonstrate that activity this regulates cell invasion metastasis to distant organs. By screening combinatorial peptide libraries, identified spectrum substrates include pro-hepatocyte growth factor (HGF). HGF activated by...
Metastatic castration-resistant prostate cancer (mCRPC) is a heterogeneous disease with diverse drivers of progression and mechanisms therapeutic resistance. We conducted deep phenotypic characterization CRPC metastases patient-derived xenograft (PDX) lines using whole genome RNA sequencing, gene set enrichment analysis immunohistochemistry. Our analyses revealed five mCRPC phenotypes based on the expression well-characterized androgen receptor (AR) or neuroendocrine (NE) genes: (i) AR-high...
Cure rates for localized high-risk prostate cancers (PCa) and some intermediate-risk PCa are frequently suboptimal with local therapy. Outcomes improved by concomitant androgen-deprivation therapy (ADT) radiation therapy, but not ADT surgery. Luteinizing hormone-releasing hormone agonist (LHRHa; leuprolide acetate) does reduce serum androgens as effectively abiraterone acetate (AA), a prodrug of abiraterone, CYP17 inhibitor that lowers testosterone (< 1 ng/dL) improves survival in metastatic...
Abstract Purpose: Neuroendocrine prostate cancer (NEPC) is an aggressive variant of that may develop de novo or as a mechanism treatment resistance. N-myc capable driving NEPC progression. Alisertib inhibits the interaction between and its stabilizing factor Aurora-A, inhibiting signaling, suppressing tumor growth. Patients Methods: Sixty men were treated with alisertib 50 mg twice daily for 7 days every 21 days. Eligibility included metastatic at least one: small-cell neuroendocrine...
Prostate cancers (PCs) with loss of the potent tumor suppressors TP53 and RB1 exhibit poor outcomes. also influence cell plasticity are frequently lost in PCs neuroendocrine (NE) differentiation. Therapeutic strategies that address these aggressive variant urgently needed. Using deep genomic profiling 410 metastatic biopsies, we determine relationships between combined PC phenotypes. Notably, 40% TP53/RB1-deficient tumors classified as AR-active adenocarcinomas, indicating NE differentiation...
Purpose To determine whether cotargeting poly (ADP-ribose) polymerase-1 plus androgen receptor is superior to inhibition in metastatic castration-resistant prostate cancer (mCRPC) and ETS fusions predict response. Patients Methods underwent site biopsy were stratified by status randomly assigned abiraterone prednisone without (arm A) or with veliparib B). Primary objectives were: confirmed prostate-specific antigen (PSA) response rate (RR) predicted Secondary safety, measurable disease RR...
Abstract Purpose: The CYP17A1 inhibitor abiraterone markedly reduces androgen precursors and is thereby effective in castration-resistant prostate cancer (CRPC). However, increases progesterone, which can activate certain mutant receptors (AR) identified previously flutamide-resistant tumors. Therefore, we sought to determine if treatment selects for progesterone-activated ARs. Experimental Design: AR was examined by targeted sequencing metastatic tumor biopsies from 18 patients with CRPC...
The neuroendocrine phenotype is associated with the development of metastatic castration-resistant prostate cancer (CRPC). Our objective was to characterize molecular features in CRPC.Expression chromogranin A (CHGA), synaptophysin (SYP), androgen receptor (AR), and prostate-specific antigen (PSA) analyzed by IHC 155 CRPC metastases from 50 patients 24 LuCaP patient-derived xenografts (PDX). Seventy-one xenograft lines were whole-genome microarrays. REST splicing verified PCR.Coexpression...
Abstract BACKGROUND: Outcomes of treatment for young men compared with older prostate cancer are poorly defined outside limited institutional series. In this study, the authors examined association between age at diagnosis and grade, stage, treatment, survival outcomes in who were diagnosed during era prostate‐specific antigen testing. METHODS: The National Cancer Institute's Surveillance, Epidemiology, End Results database was used to identify 1988 2003. Men ages 35 years 74 stratified by...
Metastases from men with castration-resistant prostate cancer (CRPC) harbor increased tumoral androgens versus untreated cancers. This may reflect steroid uptake by OATP (organic anion transporting polypeptide)/SLCO transporters. We evaluated SLCO gene expression in CRPC metastases and determined whether outcomes are associated single nucleotide polymorphisms (SNP) SLCO2B1 SLCO1B3, transporters previously shown to mediate androgen uptake.Transcripts encoding eleven genes were analyzed...
Prostate cancer (PCa) is the second most common in men. Androgen deprivation therapy (ADT) leads to tumor involution and reduction of burden. However, tumors eventually reemerge that have overcome absence gonadal androgens, termed castration resistant PCa (CRPC). Theories underlying development CRPC include androgen receptor (AR) mutation allowing for promiscuous activation by non-androgens, AR amplification overexpression leading hypersensitivity low levels, and/or tumoral uptake conversion...