A5085008756- Prostate Cancer Treatment and Research
- Cancer Genomics and Diagnostics
- Cancer, Lipids, and Metabolism
- Radiopharmaceutical Chemistry and Applications
- Genetic factors in colorectal cancer
- Molecular Biology Techniques and Applications
- Prostate Cancer Diagnosis and Treatment
- PARP inhibition in cancer therapy
- RNA modifications and cancer
- CRISPR and Genetic Engineering
- Mass Spectrometry Techniques and Applications
- Science, Research, and Medicine
- Cancer-related molecular mechanisms research
- Bladder and Urothelial Cancer Treatments
- DNA Repair Mechanisms
- Peptidase Inhibition and Analysis
- PI3K/AKT/mTOR signaling in cancer
- Renal cell carcinoma treatment
- Infectious Disease Case Reports and Treatments
- Radiation Therapy and Dosimetry
- Sexual Differentiation and Disorders
- Urinary and Genital Oncology Studies
- Multiple Myeloma Research and Treatments
- Cancer Immunotherapy and Biomarkers
- Ubiquitin and proteasome pathways
University of British Columbia
2018-2025
The Prostate Centre
2018-2023
No consensus strategies exist for prognosticating metastatic castration-resistant prostate cancer (mCRPC). Circulating tumor DNA fraction (ctDNA%) is increasingly reported by commercial and laboratory tests but its utility risk stratification unclear. Here, we intersect ctDNA%, treatment outcomes, clinical characteristics across 738 plasma samples from 491 male mCRPC patients two randomized multicentre phase II trials a prospective province-wide blood biobanking program. ctDNA% correlates...
Abstract Purpose: DNA damage repair (DDR) defects are common across cancer types and can indicate therapeutic vulnerability. Optimal exploitation of DDR in prostate requires new diagnostic strategies a better understanding associated clinical genomic features. Experimental Design: We performed targeted sequencing 1,615 plasma cell-free samples from 879 patients with metastatic cancer. Depth-based copy-number calls heterozygous SNP imbalance were leveraged to expose DDR-mutant allelic...
Abstract Purpose: Cross-resistance renders multiple lines of androgen receptor (AR) signaling inhibitors increasingly futile in metastatic castration-resistant prostate cancer (mCRPC). We sought to determine acquired genomic contributors cross-resistance. Experimental Design: collected 458 serial plasma cell-free DNA samples at baseline and progression timepoints from 202 patients with mCRPC receiving sequential AR (abiraterone enzalutamide) a randomized phase II clinical trial...
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 Purpose: Androgen receptor pathway inhibitors (ARPI) are standard of care for treatment-naïve metastatic castration-resistant prostate cancer (mCRPC), but rapid resistance is common. Early identification will improve management strategies. We investigated whether changes in circulating tumor DNA (ctDNA) fraction during ARPI treatment linked with mCRPC clinical outcomes. Experimental Design: Plasma cell-free was collected from 81 patients at baseline and after 4 weeks first-line two...
Significant progress has been made in genetic and genomic testing for prostate cancer across the disease spectrum. Molecular profiling is increasingly relevant routine clinical management, fueled part by advancements technology integration of biomarkers into trials. In metastatic cancer, defects DNA damage response genes are now established predictors benefit to US Food Drug Administration-approved poly (ADP-ribose) polymerase inhibitors immune checkpoint inhibitors, trials actively...
Abstract Small‐cell prostate carcinoma (SCPC) is an aggressive malignancy that managed similarly to small‐cell lung cancer. SCPC can evolve from adenocarcinoma in response androgen deprivation therapy, but, rare cases, present at initial cancer diagnosis. The molecular aetiology of de novo incompletely understood, owing the scarcity tumour tissue and short life‐expectancy patients. Through a retrospective search our regional oncology pharmacy database, we identified 18 patients diagnosed...
<div>Abstract<p>Cell phenotype underlies prostate cancer presentation and treatment resistance can be regulated by epigenomic features. However, the osteotropic tendency of limits access to metastatic tissue, meaning most prior insights into chromatin biology are from preclinical models that do not fully represent disease complexity. Noninvasive immunoprecipitation histones in plasma cell–free DNA (cfDNA) humans may enable capture disparate phenotypes. In this study, we analyzed...
<p>Supplementary Figures 1-12 with embedded captions.</p>
<p>Supplementary Figures 1-12 with embedded captions.</p>
189 Background: Patients (pts) with metastatic prostate cancer and liver metastases have poor prognosis, but clinicogenomic analyses are limited. We examined the clinical genomic features of a cohort (PCLM). Methods: Pts were identified from prospective population-based biobank in British Columbia, Canada. Eligible pts had PCLM on imaging prior to any line treatment. collated outcomes cell-free DNA (cfDNA) sequencing results including circulating tumor fraction (ctDNA%) alterations. Results:...
To determine the performance of a multi-gene copy number variation (MG-CNV) risk score in metastatic tissue and plasma biospecimens from treatment-naïve castrate-resistant prostate cancer (mCRPC) patients for prediction clinical outcomes. mCRPC cell-free DNA (cfDNA) biospecimen sequencing results obtained publicly accessed cohorts dbGaP, cBioPortal, an institutional cohort were used to develop MG-CNV derived gains AR, MYC, COL22A1, PIK3CA, PIK3CB, NOTCH1 losses TMPRSS2, NCOR1, ZBTB16, TP53,...
Specific classes of DNA damage repair (DDR) defect can drive sensitivity to emerging therapies for metastatic prostate cancer. However, biomarker approaches based on DDR gene sequencing do not accurately predict deficiency or treatment benefit. Somatic alteration signatures may identify but historically require whole-genome tumour tissue. We assembled whole-exome data 155 high ctDNA fraction plasma cell-free and matched leukocyte samples from patients with bladder Labels alterations were...
PURPOSE Pulmonary involvement is rare in metastatic hormone-sensitive prostate cancer (mHSPC) that recurs after treatment for localized disease. Guidelines recommend intensive systemic therapy, similar to patients with liver metastases, but some lung-recurrent mHSPC may have good outcomes. Genomic features of lung metastases clarify disease aggression, are poorly understood since biopsy rarely performed. We present a comparative assessment genomic drivers and heterogeneity metachronous...
Cell phenotype underlies prostate cancer presentation and treatment resistance can be regulated by epigenomic features. However, the osteotropic tendency of limits access to metastatic tissue, meaning most prior insights into chromatin biology are from preclinical models that do not fully represent disease complexity. Noninvasive immunoprecipitation histones in plasma cell-free humans may enable capture disparate phenotypes. Here, we analyzed activating promoter- enhancer-associated H3K4me2...