Alan Ashworth
A5058973407- PARP inhibition in cancer therapy
- CRISPR and Genetic Engineering
- DNA Repair Mechanisms
- Cancer Genomics and Diagnostics
- Epigenetics and DNA Methylation
- BRCA gene mutations in cancer
- Chromatin Remodeling and Cancer
- Lung Cancer Research Studies
- Peptidase Inhibition and Analysis
- Glioma Diagnosis and Treatment
- Monoclonal and Polyclonal Antibodies Research
- Immunotherapy and Immune Responses
- Protein Degradation and Inhibitors
- Fibroblast Growth Factor Research
- Prostate Cancer Treatment and Research
- Ovarian cancer diagnosis and treatment
- Click Chemistry and Applications
- Cancer-related Molecular Pathways
- Neuroendocrine Tumor Research Advances
- Cancer Cells and Metastasis
- Molecular Biology Techniques and Applications
- Cancer Mechanisms and Therapy
- Cancer Immunotherapy and Biomarkers
- Glycosylation and Glycoproteins Research
- Kruppel-like factors research
UCSF Helen Diller Family Comprehensive Cancer Center
2016-2025
University of California, San Francisco
2016-2025
Manchester University NHS Foundation Trust
2024
Breast Cancer Now
2012-2023
Institute of Cancer Research
2012-2023
Breast Cancer Research Foundation
2004-2023
City College of San Francisco
2016-2023
Breakthrough
2005-2023
Pancreatic Cancer Action Network
2021-2023
Quantitative BioSciences
2020-2023
The inhibition of poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) is a potential synthetic lethal therapeutic strategy for the treatment cancers with specific DNA-repair defects, including those arising in carriers BRCA1 or BRCA2 mutation. We conducted clinical evaluation humans olaparib (AZD2281), novel, potent, orally active PARP inhibitor.This was phase 1 trial that included analysis pharmacokinetic and pharmacodynamic characteristics olaparib. Selection aimed at having study...
Prostate cancer is a heterogeneous disease, but current treatments are not based on molecular stratification. We hypothesized that metastatic, castration-resistant prostate cancers with DNA-repair defects would respond to poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibition olaparib.
Abstract Deficiency in either of the breast cancer susceptibility proteins BRCA1 or BRCA2 induces profound cellular sensitivity to inhibition poly(ADP-ribose) polymerase (PARP) activity. We hypothesized that critical role and repair double-strand breaks by homologous recombination (HR) was underlying reason for this sensitivity. Here, we examine effects deficiency several involved HR on PARP inhibition. show RAD51, RAD54, DSS1, RPA1, NBS1, ATR, ATM, CHK1, CHK2, FANCD2, FANCA, FANCC such This...
Members of the Rho family small guanosine triphosphatases (GTPases) regulate organization actin cytoskeleton; controls assembly stress fibers and focal adhesion complexes, Rac regulates filament accumulation at plasma membrane to produce lamellipodia ruffles, Cdc42 stimulates formation filopodia. When microinjected into quiescent fibroblasts, Rho, Rac, stimulated cell cycle progression through G1 subsequent DNA synthesis. Furthermore, microinjection dominant negative forms or inhibitor C3...
Purpose Selective tumor cell cytotoxicity can be achieved through a synthetic lethal strategy using poly(ADP)-ribose polymerase (PARP) inhibitor therapy in BRCA1/2 mutation carriers whom cells have defective homologous recombination (HR) DNA repair. Platinum-based chemotherapy responses correlate with HR repair capacity. Olaparib is potent, oral PARP that well tolerated, antitumor activity carriers. Patients and Methods BRCA1/2-mutated ovarian cancer were treated olaparib within...
Abstract Purpose: PARP1/2 inhibitors are a class of anticancer agents that target tumor-specific defects in DNA repair. Here, we describe BMN 673, novel, highly potent inhibitor with favorable metabolic stability, oral bioavailability, and pharmacokinetic properties. Experimental Design: Potency selectivity 673 was determined by biochemical assays. Anticancer activity either as single-agent or combination other antitumor evaluated both vitro xenograft cancer models. Results: is (PARP1 IC50 =...
ABSTRACT An outbreak of the novel coronavirus SARS-CoV-2, causative agent COVID-19 respiratory disease, has infected over 290,000 people since end 2019, killed 12,000, and caused worldwide social economic disruption 1,2 . There are currently no antiviral drugs with proven efficacy nor there vaccines for its prevention. Unfortunately, scientific community little knowledge molecular details SARS-CoV-2 infection. To illuminate this, we cloned, tagged expressed 26 29 viral proteins in human...