A5010259733- Prostate Cancer Treatment and Research
- Cancer Genomics and Diagnostics
- Histone Deacetylase Inhibitors Research
- Cancer, Hypoxia, and Metabolism
- Radiopharmaceutical Chemistry and Applications
- PARP inhibition in cancer therapy
- Molecular Biology Techniques and Applications
- Genetic factors in colorectal cancer
- Protein Degradation and Inhibitors
- Cancer-related molecular mechanisms research
- RNA modifications and cancer
- Ubiquitin and proteasome pathways
- Epigenetics and DNA Methylation
- Pancreatic and Hepatic Oncology Research
- Peptidase Inhibition and Analysis
- MicroRNA in disease regulation
- Estrogen and related hormone effects
- Cancer, Lipids, and Metabolism
- Cancer Immunotherapy and Biomarkers
- Chemical Synthesis and Analysis
- DNA Repair Mechanisms
- Tannin, Tannase and Anticancer Activities
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Renal cell carcinoma treatment
- Urinary and Genital Oncology Studies
Medical College of Wisconsin
2022-2024
Fred Hutch Cancer Center
2016-2024
Medical College of Wisconsin Cancer Center
2024
Prostate Cancer UK
2024
University of Washington
2016-2023
Clinical Research Management
2021
University of Washington Medical Center
2020
Seattle University
2016-2020
Indian Statistical Institute
2012-2019
Memorial Sloan Kettering Cancer Center
2016
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.
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;...
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...
Abstract Lineage plasticity, the ability of a cell to alter its identity, is an increasingly common mechanism adaptive resistance targeted therapy in cancer. An archetypal example development neuroendocrine prostate cancer (NEPC) after treatment adenocarcinoma (PRAD) with inhibitors androgen signaling. NEPC aggressive variant that aberrantly expresses genes characteristic (NE) tissues and no longer depends on androgens. Here, we investigate epigenomic basis this by profiling histone...
Abstract Cell-free DNA (cfDNA) has the potential to inform tumor subtype classification and help guide clinical precision oncology. Here we develop Griffin, a framework for profiling nucleosome protection accessibility from cfDNA study phenotype of tumors using as low 0.1x coverage whole genome sequencing data. Griffin employs GC correction procedure tailored variable fragment sizes, which generates better representation chromatin improves accuracy cancer detection classification. We...
<h3>Importance</h3> DNA damage repair (DDR) gene mutations represent actionable alterations that can guide precision medicine strategies for advanced prostate cancer. However, acquisition of contemporary tissue samples molecular testing be a barrier to deploying approaches. We hypothesized most DDR truncal events in cancer and primary would faithfully reflect found cell-free circulating tumor (ctDNA) and/or metastatic tissue. <h3>Objective</h3> To assess concordance between metastases or...
Abstract Purpose: Neuroendocrine prostate cancer (NEPC) is an aggressive form of castration-resistant (CRPC) for which effective therapies are lacking. We previously identified carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) as a promising NEPC surface antigen. Here we investigated the scope CEACAM5 expression in end-stage cancer, basis enrichment NEPC, and therapeutic potential antibody–drug conjugate labetuzumab govitecan cancer. Experimental Design: The other...
Advanced prostate cancers comprise distinct phenotypes, but tumor classification remains clinically challenging. Here, we harnessed circulating DNA (ctDNA) to study phenotypes by ascertaining nucleosome positioning patterns associated with transcription regulation. We sequenced plasma ctDNA whole genomes from patient-derived xenografts representing a spectrum of androgen receptor active (ARPC) and neuroendocrine (NEPC) cancers. Nucleosome transcriptional activity were reflected in at regions...
Abstract Therapeutic approaches targeting proteins on the surface of cancer cells have emerged as an important strategy for precision oncology. To capitalize potential impact drugs proteins, detailed knowledge about expression patterns target in tumor tissues is required. In castration-resistant prostate (CRPC), agents prostate-specific membrane antigen (PSMA) demonstrated clinical activity. However, PSMA lost a significant number CRPC tumors. The identification additional cell targets...
Abstract Purpose: To determine whether metastatic castration–resistant prostate cancers (mCRPC) partition into molecular phenotypes corresponding to intrinsic differentiation states and ascertain these subtypes exhibit specific druggable features associate with treatment outcomes. Experimental Design: We used RNAseq, digital spatial profiling, histological assessments from biopsies patient-derived xenografts segregate mCRPCs defined by the PAM50 breast cancer classification algorithm....
BACKGROUND. Little is known about the genomic differences between metastatic lower tract urothelial carcinoma (LTUC) and upper (UTUC). We compare features of primary UTUC LTUC tumors in a cohort patients with end-stage disease.
Prostate cancer (PC) is driven by androgen receptor (AR) activity, a master regulator of prostate development and homeostasis. Frontline therapies for metastatic PC deprive the AR activating ligands testosterone (T) dihydrotestosterone (DHT) limiting their biosynthesis or blocking binding. Notably, signaling dichotomous, inducing growth at lower activity levels, while suppressing higher levels. Recent clinical studies have exploited this effect administration supraphysiological...
Deregulation of miRNA expression may contribute to tumorigenesis and other patho-physiology associated with cancer. Using TLDA, 762 miRNAs was checked in 18 pairs gingivo buccal cancer-adjacent control tissues. Expression significantly deregulated further validated cancer examined two types precancer (leukoplakia lichen planus) tissues by primer-specific TaqMan assays. Biological implications these were assessed bioinformatically. hsa-miR-1293, hsa-miR-31, hsa-miR-31* hsa-miR-7 up-regulated...
Abstract Oral cancer generally progresses from precancerous lesions such as leukoplakia (LK), lichen planus (LP) and oral submucous fibrosis (OSMF). Since few of these precancers progress to cancers; it is worth identify biological molecules that may play important roles in progression. Here, expression deregulation 7 miRNAs ( mir204, mir31, mir31*, mir133a, mir7, mir206 mir1293 ) their possible target genes 23 cancers, 18 LK, 12 LP, OSMF tissues compared 20 healthy was determined by qPCR...
Cancers with homology-directed DNA repair (HRR) deficiency exhibit high response rates to poly(ADP-ribose) polymerase inhibitors (PARPi) and platinum chemotherapy. Though mutations disrupting BRCA1 BRCA2 associate HRR (HRRd), patterns of genomic aberrations mutation signatures may be more sensitive specific indicators compromised repair. Here, we evaluated whole-exome sequences from 418 metastatic prostate cancers (mPCs) determined that one-fifth exhibited characteristics HRRd included...
Genetic variations at microRNA and processing genes are known to confer risk of cancer in different populations. Here, we studied eight (miRNA) four miRNA 452 controls 451 oral patients by TaqMan genotyping assays. Variant allele-containing genotypes mir-196a2 variant allele homozygous genotype Ran increased the significantly [adjusted odds ratio (OR) (95 % confidence interval (CI)) = 1.3 (1–1.7) 2.3 (1.1–4.6), respectively]. Conversely, mir-34b Gemin3 reduced OR CI) 0.7 (0.5–0.9) 0.6...
ABSTRACT Modern bioinformatics studies often involve numerous simultaneous statistical tests, increasing the risk of false discoveries. To control discovery rate (FDR), these typically employ a method called Benjamini–Hochberg (BH) method. Often, BH approach tends to be overly conservative and overlooks valuable biological insights associated with data structures, particularly those groups. Group structures can manifest when closely located genomic coordinates are functionally active related...
Plasma-based cell-free DNA is an attractive biospecimen for assessing somatic mutations due to minimally-invasive real-time sampling. However, next generation sequencing (NGS) of (cfDNA) may not be appropriate all patients with advanced prostate cancer (PC).Blood was obtained from PC plasma-based sequencing. UW-OncoPlex, a ∼2 Mb multi-gene NGS panel performed in the CLIA/CAP environment, optimized detecting cfDNA mutations. Tumor tissue and germline samples were sequenced comparative...
Abstract Background Pancreatic Ductal Adenocarcinoma (PDAC) is a cancer of the exocrine pancreas and 5-year survival rates remain constant at 7%. Along with PDAC, Periampullary (PAC) accounts for 0.5–2% all gastrointestinal malignancies. Genomic observations were well concluded PDAC PACs in western countries but no reports are available from India till now. Methods Targeted Next Generation Sequencing performed 8 (5 3 PAC) tumour normal pairs, using panel 412 related genes. Primary findings...