A5052694721- Prostate Cancer Treatment and Research
- Cancer, Lipids, and Metabolism
- Radiopharmaceutical Chemistry and Applications
- Protein Degradation and Inhibitors
- Histone Deacetylase Inhibitors Research
- Cancer, Hypoxia, and Metabolism
- Prostate Cancer Diagnosis and Treatment
- Cancer Genomics and Diagnostics
- Ubiquitin and proteasome pathways
- Estrogen and related hormone effects
- Epigenetics and DNA Methylation
- Cancer Immunotherapy and Biomarkers
- Advanced Breast Cancer Therapies
- Hormonal and reproductive studies
- Peptidase Inhibition and Analysis
- PARP inhibition in cancer therapy
- Mechanisms of cancer metastasis
- Multiple Myeloma Research and Treatments
- Immunotherapy and Immune Responses
- Cancer-related gene regulation
- Glutathione Transferases and Polymorphisms
- Cancer Treatment and Pharmacology
- Kruppel-like factors research
- Tannin, Tannase and Anticancer Activities
- Bone health and treatments
University of Michigan
2019-2025
Michigan Center for Translational Pathology
2025
Oregon Health & Science University
2013-2022
OHSU Knight Cancer Institute
2011-2022
Michigan Medicine
2022
U-M Rogel Cancer Center
2021
University of California, Santa Cruz
2018
Sidney Kimmel Comprehensive Cancer Center
2004-2018
University of California, San Francisco
2009-2018
Memorial Sloan Kettering Cancer Center
2009-2018
Purpose The prevalence and features of treatment-emergent small-cell neuroendocrine prostate cancer (t-SCNC) are not well characterized in the era modern androgen receptor (AR)-targeting therapy. We sought to characterize clinical genomic t-SCNC a multi-institutional prospective study. Methods Patients with progressive, metastatic castration-resistant (mCRPC) underwent tumor biopsy were followed for survival. Metastatic specimens independent, blinded pathology review along RNA/DNA...
Background: Real-time knowledge of the somatic genome can influence management patients with metastatic castration-resistant prostate cancer (mCRPC). While routine tissue biopsy is challenging in mCRPC, plasma circulating tumor DNA (ctDNA) has emerged as a minimally invasive tool to sample genome. However, no systematic comparisons matched "liquid" and "solid" biopsies have been performed that would enable ctDNA profiling replace need for direct sampling. Methods: We targeted sequencing...
// Julie N. Graff 1,2 , Joshi J. Alumkal 1 Charles G. Drake 3 George V. Thomas 4 William L. Redmond 5 Mohammad Farhad 5,6 Jeremy P. Cetnar Frederick S. Ey Raymond C. Bergan Rachel Slottke and Tomasz M. Beer Division of Hematology/Oncology, Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA 2 VA Portland Care System, Sidney Kimmel Comprehensive Center the Brady Urological Johns Hopkins University School Medicine, Baltimore, MD, Pathology Laboratory Robert W....
Approximately 20% of metastatic prostate cancers harbor mutations in genes required for DNA repair by homologous recombination (HRR) such as
Significance Medical castration or interference with androgen receptor (AR) function is the principal treatment for advanced prostate cancer. However, progression universal, and therapies following emergence of resistance do not offer durable control disease. Lysine-specific demethylase 1 (LSD1) an important regulator gene expression, including in Here, we show that LSD1 highly expressed tumors patients lethal castration-resistant cancer (CRPC) promotes AR-independent survival CRPC cells a...
High consumption of cruciferous vegetables is associated with a reduced risk prostate cancer in epidemiological studies. There preliminary evidence that sulforaphane, derived from glucoraphanin found number crucifers, may prevent and induce regression other malignancies preclinical models, but the mechanisms explain these effects are not fully defined. Recent reports show sulforaphane impair growth through inhibition histone deacetylases, which up-regulated cancer. Indeed, one enzymes,...
Significance The androgen receptor (AR) antagonist enzalutamide is one of the principal treatments for men with metastatic castration-resistant prostate cancer. However, not all patients respond, and de novo resistance mechanisms are largely unknown. To clarify that contribute to resistance, we conducted a single-arm clinical trial. Metastatic tissue biopsies were required prior study entry so could attempt identify molecular features associated resistance. Transcriptional profiling...
The androgen receptor (AR) is the principal therapeutic target in prostate cancer. For past 70 years, deprivation therapy (ADT) has been major focus. However, some patients do not benefit, and those tumors that initially respond to ADT eventually progress. One recently described mechanism of such an effect growth survival-promoting effects AR are exerted independently ligands, testosterone dihydrotestosterone. specific ligand-independent genes account for this were well characterized. We...
Apalutamide is a potent androgen receptor (AR) antagonist that targets the AR ligand-binding domain and prevents nuclear translocation, DNA binding, transcription of gene targets. To evaluate activity safety apalutamide in patients with high-risk nonmetastatic castration-resistant prostate cancer (nmCRPC). We conducted multicenter phase 2 study nmCRPC high risk for progression (prostate-specific antigen [PSA] ≥8 ng/ml or PSA doubling time [PSA DT] ≤10 mo). Patients received 240 mg/d while...
ZEN-3694 is a bromodomain extraterminal inhibitor (BETi) with activity in androgen-signaling (ASI)-resistant models. The safety and efficacy of plus enzalutamide was evaluated phase Ib/IIa study metastatic castration-resistant prostate cancer (mCRPC).
Background Checkpoint inhibitors can induce profound anticancer responses, but programmed cell death protein-1 (PD-1) inhibition monotherapy has shown minimal activity in prostate cancer. A published report showed that men with cancer who were resistant to the second-generation androgen receptor inhibitor enzalutamide had increased death-ligand 1 (PD-L1) expression on circulating antigen-presenting cells. We hypothesized addition of PD-1 these patients could a meaningful response. Methods...
Metastatic castration resistant prostate cancer (mCRPC) is incurable and progression after drugs that target the androgen receptor-signaling axis inevitable. Thus, there an urgent need to develop more effective treatments beyond hormonal manipulation. We sought identify activated kinases in mCRPC as therapeutic targets for existing, approved agents, with goal of identifying candidate rapid translation into proof concept Phase II trials mCRPC. To evidence activation druggable these patients,...
Analysis of DNA methylation is a valuable tool to understand disease progression and increasingly being used create diagnostic prognostic clinical biomarkers. While conversion cytosine 5-methylcytosine (5mC) commonly results in transcriptional repression, further 5-hydroxymethylcytosine (5hmC) associated with activation. Here we perform the first study integrating whole-genome 5hmC DNA, 5mC, transcriptome sequencing samples benign, localized, advanced prostate cancer. shown mark activation...
Abstract Decades of research into the molecular mechanisms cancer and development novel therapeutics have yielded a number remarkable successes. However, our ability to broadly assign effective, rationally targeted therapies in personalized manner remains elusive for many patients, drug resistance persists as major problem. This is part due well-documented heterogeneity cancer, including diversity tumor cell lineages states, spectrum somatic mutations, complexity microenvironments,...