A5016703081- Cancer Genomics and Diagnostics
- PARP inhibition in cancer therapy
- Prostate Cancer Treatment and Research
- Lymphoma Diagnosis and Treatment
- Cutaneous lymphoproliferative disorders research
- PI3K/AKT/mTOR signaling in cancer
- T-cell and Retrovirus Studies
- DNA Repair Mechanisms
- Gene expression and cancer classification
- Cancer Treatment and Pharmacology
- Molecular Biology Techniques and Applications
- BRCA gene mutations in cancer
- Lung Cancer Treatments and Mutations
- Science, Research, and Medicine
- Monoclonal and Polyclonal Antibodies Research
- Cancer-related Molecular Pathways
- Cancer Research and Treatments
- Advanced Breast Cancer Therapies
- Cancer, Lipids, and Metabolism
- Cell death mechanisms and regulation
- Amyotrophic Lateral Sclerosis Research
- Microtubule and mitosis dynamics
- Cancer Cells and Metastasis
- Computational Drug Discovery Methods
- Colorectal Cancer Treatments and Studies
AstraZeneca (United Kingdom)
2016-2025
East Tennessee State University
2024
Columbia University Irving Medical Center
2022-2024
University of Iowa
2024
Western Health
2024
Columbia University
2021-2024
Pfizer (United Kingdom)
2021
National Human Genome Research Institute
2000-2021
National Institutes of Health
2001-2021
Sanofi (France)
2021
BACKGROUND: Preclinical studies and results of a phase 2 trial abiraterone olaparib suggest combined antitumor effect when the poly(adenosine diphosphate[ADP]-ribose) polymerase inhibitor is with next-generation hormonal agent to treat metastatic castration-resistant prostate cancer (mCRPC). METHODS: We conducted double-blind, 3 versus placebo in patients mCRPC first-line setting. Patients were enrolled regardless homologous recombination repair gene mutation (HRRm) status. HRRm status was...
Abstract The VIKTORY (targeted agent eValuation In gastric cancer basket KORea) trial was designed to classify patients with metastatic based on clinical sequencing and focused eight different biomarker groups (RAS aberration, TP53 mutation, PIK3CA mutation/amplification, MET amplification, overexpression, all negative, TSC2 deficient, or RICTOR amplification) assign one of the 10 associated trials in second-line (2L) treatment. Capivasertib (AKT inhibitor), savolitinib (MET selumetinib (MEK...
Despite extensive research, amyotrophic lateral sclerosis (ALS) remains a progressive and invariably fatal neurodegenerative disease. Limited knowledge of the underlying causes ALS has made it difficult to target upstream biological mechanisms disease, therapeutic interventions are usually administered relatively late in course Genetic forms offer unique opportunity for development, as genetic associations may reveal potential insights into disease etiology. also be amenable investigating...
11 Background: Preclinical studies have shown combined anti-tumor effect through interactions between poly(adenosine diphosphate–ribose) polymerase and androgen receptor signaling pathways. A Phase II trial (NCT01972217) in pts with mCRPC unselected by homologous recombination repair (HRR) status who previously received docetaxel demonstrated improved radiographic progression-free survival (rPFS) for treated ola + abi vs pbo (Clarke N, 2018). The III PROpel study (NCT03732820) evaluates the...
Abstract —Recent evidence indicates that the type of atherosclerotic plaque, rather than degree obstruction to flow, is an important determinant risk cardiovascular complications. In previous work, feasibility using MRI for characterization plaque components was shown. This study extends work all and shows accuracy this method. Twenty-two human carotid endarterectomy specimens underwent ex vivo histopathological examination. Sixty-six cross sections were matched between histopathology. each...
To maintain genome stability, cells with damaged DNA must arrest to allow repair of mutations before replication. Although several key components required elicit this have been discovered, much the pathway remains elusive. Here we report that pRB acts as a central mediator proliferative block induced by diverse range damaging stimuli. Rb −/− mouse embryo fibroblasts are defective in after γ-irradiation, UV irradiation, and treatment variety chemotherapeutic drugs. In contrast, related...
Abstract Vorinostat is a histone deacetylase inhibitor that induces differentiation, growth arrest, and/or apoptosis of malignant cells both in vitro and vivo has shown clinical responses ∼30% patients with advanced mycosis fungoides Sézary syndrome cutaneous T-cell lymphoma (CTCL). The purpose this study was to identify biomarkers predictive vorinostat response CTCL using preclinical model systems assess these samples. signal transducer activator transcription (STAT) signaling pathway...
AZD2014 is a novel, oral, m-TORC 1/2 inhibitor that has shown in vitro and vivo efficacy across range of preclinical human cancer models.A rolling six-dose escalation was performed to define an MTD (part A), at further cohort patients treated characterize toxicities perform pre- posttreatment biopsies B). administered orally twice day continuously. Flow cytometry, ELISA, immunohistochemistry were used quantify pharmacodynamic biomarkers. Pharmacokinetic analysis carried out by mass...
Abstract Liquid biopsies offer the potential to monitor cancer response and resistance therapeutics in near real-time. However, plasma cell free DNA (cfDNA) level can be low fraction of circulating tumour (ctDNA) bearing a mutation – lower still. Detection tumour-derived mutations ctDNA is thus challenging requires highly sensitive specific assays. Droplet digital PCR (ddPCR) technique that enables exquisitely detection quantification DNA/RNA markers from very limiting clinical samples,...
Abstract Purpose: Not all patients with metastatic castration-resistant prostate cancer (mCRPC) have sufficient tumor tissue available for multigene molecular testing. Furthermore, samples may fail because of difficulties within the testing procedure. Optimization screening techniques reduce failure rates; however, a need remains additional methods to detect cancers alterations in homologous recombination repair genes. We evaluated utility plasma-derived circulating DNA (ctDNA) identifying...
We previously generated a mouse model with mutation in the murine Atm gene that recapitulates many aspects of childhood neurodegenerative disease ataxia-telangiectasia. -deficient ( −/−) mice show neurological defects detected by motor function tests including rota-rod, open-field and hind-paw footprint analysis. However, no gross histological abnormalities have been observed consistently cerebellum any line −/− analyzed most laboratories. Therefore, it may be neurologic dysfunction found...
Ataxia telangiectasia (A-T) is an autosomal recessive disease characterized by normal brain development followed progressive neurodegeneration. The gene mutated in A-T (ATM) a serine protein kinase implicated cell cycle regulation and DNA repair. role of ATM the consequences its loss on neuronal survival remain unclear. We studied adult neural progenitor cells vivo vitro to define dividing postmitotic from Atm -deficient ( −/− ) mice physiologic context. demonstrate that abundant but...
Abstract Loss of PTEN protein results in upregulation the PI3K/AKT pathway, which appears dependent on PI3Kβ isoform. Inhibitors have potential to reduce growth tumors loss drives tumor progression. We developed a small-molecule inhibitor and PI3Kδ (AZD8186) assessed its antitumor activity across panel cell lines. then explored effects as single agent combination with docetaxel triple-negative breast (TNBC) prostate cancer models. In vitro, AZD8186 inhibited range Sensitivity was associated...
Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease with distinct molecular subtypes. The most established subtyping approach, the "Cell of Origin" (COO) algorithm, categorizes DLBCL into activated (ABC) and germinal center (GCB)-like subgroups through gene expression profiling. Recently developed immunohistochemical (IHC) techniques other methodologies can deliver discordant results have various technical limitations. We evaluated NanoString nCounter system to address issues...
Providers and patients encounter challenges related to the management of Variants Unknown Significance (VUS). A VUS introduces new counseling dilemmas for understanding psychosocial impact uncertain genetic test results. This descriptive study uses Mishel's theory uncertainty in illness explore experience individuals who have received a as part testing process. Semi-structured interviews were conducted with 27 adult Lynch syndrome mismatch repair genes between 2002 2013. The transcribed...
Abstract Purpose: Common resistance mechanisms to endocrine therapy (ET) in estrogen receptor (ER)–positive metastatic breast cancers include, among others, ER loss and acquired activating mutations the ligand-binding domain of gene (ESR1LBDm). ESR1 mutational mediated may be overcome by selective degraders (SERD). During first-in-human study oral SERD AZD9496, early changes circulating tumor cells (CTCs) DNA (ctDNA) were explored as potential noninvasive tools, alongside paired biopsies,...