A5062125605- Prostate Cancer Treatment and Research
- Cancer, Lipids, and Metabolism
- Prostate Cancer Diagnosis and Treatment
- Clusterin in disease pathology
- Estrogen and related hormone effects
- Cancer Genomics and Diagnostics
- Radiopharmaceutical Chemistry and Applications
- Hormonal and reproductive studies
- Heat shock proteins research
- Cancer, Hypoxia, and Metabolism
- Bladder and Urothelial Cancer Treatments
- Ubiquitin and proteasome pathways
- Molecular Biology Techniques and Applications
- Epigenetics and DNA Methylation
- Nuclear Structure and Function
- Cancer-related gene regulation
- PARP inhibition in cancer therapy
- Biomarkers in Disease Mechanisms
- Cell Adhesion Molecules Research
- RNA Research and Splicing
- Endoplasmic Reticulum Stress and Disease
- Cancer-related Molecular Pathways
- Mass Spectrometry Techniques and Applications
- Autophagy in Disease and Therapy
- Cell death mechanisms and regulation
University of British Columbia
2016-2025
Vancouver General Hospital
2013-2024
The Prostate Centre
2008-2024
Mayo Clinic Hospital
2024
UK Health Security Agency
2024
Zymeworks (Canada)
2023
UC Davis Comprehensive Cancer Center
2022
University of California, Davis
2017-2022
University of Port Harcourt Teaching Hospital
2022
Marqués de Valdecilla University Hospital
2022
Neuroendocrine prostate cancer (NEPC) is an aggressive subtype of that most commonly evolves from preexisting adenocarcinoma (PCA). Using Next Generation RNA-sequencing and oligonucleotide arrays, we profiled 7 NEPC, 30 PCA, 5 benign tissue (BEN), validated findings on tumors a large cohort patients (37 169 22 BEN) using IHC FISH. We discovered significant overexpression gene amplification AURKA MYCN in 40% NEPC 5% respectively, evidence they cooperate to induce neuroendocrine phenotype...
Although systemic androgen deprivation prolongs life in advanced prostate cancer, remissions are temporary because patients almost uniformly progress to a state of castration-resistant cancer (CRPC) as indicated by recurring PSA. This complex process progression does not seem be stochastic the timing and phenotype highly predictable, including observation that most androgen-regulated genes reactivated despite castrate levels serum androgens. Recent evidence indicates intraprostatic androgens...
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...
In advanced prostate cancer (APC), successful drug development as well advances in imaging and molecular characterisation have resulted multiple areas where there is lack of evidence or low level evidence. The Advanced Prostate Cancer Consensus Conference (APCCC) 2017 addressed some these topics. To present the report APCCC 2017. Ten important controversy APC management were identified: high-risk localised locally cancer; “oligometastatic” castration-naïve castration-resistant role APC;...
Pancreatic cancer is a disease with an extremely poor prognosis. Tumor protein 53-induced nuclear 1 ( TP53INP1 ) proapoptotic stress-induced p53 target gene. In this article, we show by immunohistochemical analysis that expression dramatically reduced in pancreatic ductal adenocarcinoma (PDAC) and decrease occurs early during development. reexpression the cancer-derived cell line MiaPaCa2 strongly its capacity to form s.c., i.p., intrapancreatic tumors nude mice. This anti-tumoral is, at...
Abstract Androgen deprivation therapy (ADT) remains the primary treatment for advanced prostate cancer. The efficacy of ADT has not been rigorously evaluated by demonstrating suppression prostatic androgen activity at target tissue and molecular level. We determined consistency medical castration in suppressing levels androgen-regulated gene expression. expression (by microarray profiling, quantitative reverse transcription-PCR, immunohistochemistry) were measured samples from a clinical...
Abstract A model of human prostate cancer was established to study cellular interaction between and bone stroma in vivo . In this model, subcutaneous co‐injection 2 non‐tumorigenic cell lines‐LNCaP, a line, MS, stromal line‐into intact adult male mice resulted formation carcinomas that secreted prostate‐specific antigen (PSA), clinically useful serum marker. castrated hosts, upon with fibroblasts, we observed the progression these tumors from an androgen‐dependent (AD) androgen‐independent...
Abstract Primary resistance to androgen receptor (AR)–directed therapies in metastatic castration-resistant prostate cancer (mCRPC) is poorly understood. We randomized 202 patients with treatment-naïve mCRPC abiraterone or enzalutamide and performed whole-exome deep targeted 72-gene sequencing of plasma cell-free DNA prior therapy. For these agents, which have never been directly compared, time progression was similar. Defects BRCA2 ATM were strongly associated poor clinical outcomes...
PTEN loss or PI3K/AKT signaling pathway activation correlates with human prostate cancer progression and metastasis. However, in preclinical murine models, deletion of Pten alone fails to mimic the significant metastatic burden that frequently accompanies end stage disease. To identify additional alterations cooperate progression, we surveyed tissue microarrays found RAS/MAPK is significantly elevated both primary lesions. In an attempt model this event, crossed conditional activatable...
Although novel agents targeting the androgen-androgen receptor (AR) axis have altered treatment paradigm of metastatic castration-resistant prostate cancer (mCRPC), development therapeutic resistance is inevitable. In this study, we examined whether AR gene aberrations detectable in circulating cell-free DNA (cfDNA) are associated with to abiraterone acetate and enzalutamide mCRPC patients.Plasma was collected from 62 patients ceasing (n = 29), 19), or other 14) due disease progression....
Abstract Mechanisms controlling the emergence of lethal neuroendocrine prostate cancer (NEPC), especially those that are consequences treatment-induced suppression androgen receptor (AR), remain elusive. Using a unique model AR pathway inhibitor–resistant cancer, we identified AR-dependent control neural transcription factor BRN2 (encoded by POU3F2) as major driver NEPC and aggressive tumor growth, both in vitro vivo. Mechanistic studies showed directly suppresses transcription, which is...
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...
Standardized and reproducible preclinical models that recapitulate the dynamics of prostate cancer are urgently needed. We established a bank transplantable patient-derived xenografts capture biologic molecular heterogeneity currently confounding prognostication therapy development. Xenografts preserved histopathology, genome architecture, global gene expression donor tumors. Moreover, their aggressiveness matched patient observations, response to androgen withdrawal correlated with tumor...
// Valentina R. Minciacchi 1 , Sungyong You Cristiana Spinelli Samantha Morley 2 Mandana Zandian Paul-Joseph Aspuria 3 Lorenzo Cavallini 1,4 Chiara Ciardiello 1,5 Mariana Reis Sobreiro Matteo Morello Geetanjali Kharmate 6 Su Chul Jang 7 Dae-Kyum Kim Elham Hosseini-Beheshti Emma Tomlinson Guns Martin Gleave Yong Song Gho Suresh Mathivanan 8 Wei Yang Michael Freeman 1,2 and Dolores Di Vizio Division of Cancer Biology Therapeutics, Departments Surgery, Biomedical Sciences Pathology Laboratory...
The molecular landscape underpinning response to the androgen receptor (AR) antagonist enzalutamide in patients with metastatic castration-resistant prostate cancer (mCRPC) is undefined. Consequently, there an urgent need for practical biomarkers guide therapy selection and elucidate resistance. Although tissue biopsies are impractical perform routinely majority of mCRPC, analysis plasma cell-free DNA (cfDNA) has recently emerged as a minimally invasive method explore tumor...
Drug discovery is a rigorous process that requires billion dollars of investments and decades research to bring molecule "from bench bedside". While virtual docking can significantly accelerate the drug discovery, it ultimately lags current rate expansion chemical databases already exceed billions molecular records. This recent surge small molecules availability presents great opportunities, but also demands much faster screening protocols. In order address this challenge, we herein...
Innovations in treatments, imaging, and molecular characterisation advanced prostate cancer have improved outcomes, but there are still many aspects of management that lack high-level evidence to inform clinical practice. The Advanced Prostate Cancer Consensus Conference (APCCC) 2019 addressed some these topics supplement guidelines based on level 1 evidence.To present the results from APCCC 2019.Similar prior conferences, experts identified 10 important areas controversy regarding cancer:...