A5045263771- Cancer Genomics and Diagnostics
- Lung Cancer Treatments and Mutations
- DNA Repair Mechanisms
- Cancer Immunotherapy and Biomarkers
- RNA modifications and cancer
- CRISPR and Genetic Engineering
- PARP inhibition in cancer therapy
- Telomeres, Telomerase, and Senescence
- Carcinogens and Genotoxicity Assessment
- Ovarian cancer diagnosis and treatment
- BRCA gene mutations in cancer
- Cancer-related Molecular Pathways
- Epigenetics and DNA Methylation
- Gastric Cancer Management and Outcomes
- HER2/EGFR in Cancer Research
- Cancer Research and Treatments
- Virus-based gene therapy research
- Colorectal Cancer Treatments and Studies
- Molecular Biology Techniques and Applications
- Genetic factors in colorectal cancer
- Cancer Cells and Metastasis
- Lymphoma Diagnosis and Treatment
- Ferroptosis and cancer prognosis
- Pancreatic and Hepatic Oncology Research
- Renal cell carcinoma treatment
AstraZeneca (United States)
2016-2025
AstraZeneca (Japan)
2022-2024
Kala Pharmaceuticals (United States)
2020-2023
AstraZeneca (Brazil)
2014-2023
AstraZeneca (United Kingdom)
2012-2021
London North West Healthcare NHS Trust
2018
Olivia Newton-John Cancer Wellness & Research Centre
2017
St George Hospital
2017
St Petersburg University
2017
Memorial Sloan Kettering Cancer Center
2017
A strong candidate for the 17q-linked BRCA1 gene, which influences susceptibility to breast and ovarian cancer, has been identified by positional cloning methods. Probable predisposing mutations have detected in five of eight kindreds presumed segregate alleles. The include an 11-base pair deletion, a 1-base insertion, stop codon, missense substitution, inferred regulatory mutation. gene is expressed numerous tissues, including ovary, encodes predicted protein 1863 amino acids. This contains...
Sir2 is a NAD+-dependent protein deacetylase that extends lifespan in yeast and worms. This study examines seven human proteins homologous to (SIRT1 through SIRT7) for cellular localization, expression profiles, deacetylation activity, effects on cell lifespan. We found that: 1) three nuclear SIRT (SIRT1, SIRT6, show different subnuclear localizations: SIRT6 SIRT7 are associated with heterochromatic regions nucleoli, respectively, where functions; 2) SIRT3, SIRT4, SIRT5 localized...
Loss of heterozygosity data from familial tumors suggest that BRCA1 , a gene confers susceptibility to ovarian and early-onset breast cancer, encodes tumor suppressor. The region is also subject allelic loss in sporadic cancers, an indication mutations may occur somatically these tumors. coding was examined for primary show allele at the locus. Mutations were detected 3 32 1 12 carcinomas; all four germline alterations occurred cancers. These results mutation not be critical development...
Accurate variant calling in next generation sequencing (NGS) is critical to understand cancer genomes better. Here we present VarDict, a novel and versatile caller for both DNA- RNA-sequencing data. VarDict simultaneously calls SNV, MNV, InDels, complex structural variants, expanding the detected genetic driver landscape of tumors. It performs local realignments on fly more accurate allele frequency estimation. performance scales linearly depth, enabling ultra-deep used explore tumor...
Purpose Third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have demonstrated potent activity against TKI resistance mediated by EGFR T790M. We studied whether noninvasive genotyping of cell-free plasma DNA (cfDNA) is a useful biomarker for prediction outcome from third-generation EGFR-TKI, osimertinib. Methods Plasma was collected all patients in the first-in-man study Patients who were included had acquired EGFR-TKI and evidence common...
Purpose The AURA study ( ClinicalTrials.gov identifier: NCT01802632) included two cohorts of treatment-naïve patients to examine clinical activity and safety osimertinib (an epidermal growth factor receptor [EGFR] –tyrosine kinase inhibitor selective for EGFR–tyrosine sensitizing [ EGFRm] EGFR T790M resistance mutations) as first-line treatment EGFR-mutated advanced non–small-cell lung cancer (NSCLC). Patients Methods Sixty with locally or metastatic EGFRm NSCLC received 80 160 mg once daily...
ObjectivesTo assess the ability of different technology platforms to detect epidermal growth factor receptor (EGFR) mutations, including T790M, from circulating tumor DNA (ctDNA) in advanced non-small cell lung cancer (NSCLC) patients.Materials and methodsA comparison multiple for detecting EGFR mutations plasma ctDNA was undertaken. Plasma samples were collected patients entering ongoing AURA trial (NCT01802632), investigating safety, tolerability, efficacy AZD9291 with EGFR-sensitizing...
Background Tumor mutational burden (TMB), defined as the number of somatic mutations per megabase interrogated genomic sequence, demonstrates predictive biomarker potential for identification patients with cancer most likely to respond immune checkpoint inhibitors. TMB is optimally calculated by whole exome sequencing (WES), but next-generation targeted panels provide estimates in a time-effective and cost-effective manner. However, differences panel size gene coverage, addition underlying...
Abstract Despite the existence of morphologically indistinguishable disease, patients with advanced ovarian tumors display a broad range survival end points. We hypothesize that gene expression profiling can identify prognostic signature accounting for these distinct clinical outcomes. To resolve survival-associated loci, was completed an extensive set 185 (90 optimal/95 suboptimal) primary using Affymetrix human U133A microarray. Cox regression analysis identified probe sets associated in...
Abstract Purpose: The presence of similar histologic subtypes epithelial ovarian and endometrial cancers has long been noted, although the relevance this finding to pathogenesis clinical management is unclear. Despite characteristics, ovary endometrium are treated according organ origin. This study compares gene expression profiles analogous using same genomic platform determine similarities differences between these tumors. Experimental Design: Gene 75 (endometrioid, serous, clear cell)...
BackgroundBRCA1 and BRCA2 (BRCA1/2)-deficient tumors display impaired homologous recombination repair (HRR) enhanced sensitivity to DNA damaging agents or poly(ADP-ribose) polymerase (PARP) inhibitors (PARPi). Their efficacy in germline BRCA1/2 (gBRCA1/2)-mutated metastatic breast cancers has been recently confirmed clinical trials. Numerous mechanisms of PARPi resistance have described, whose relevance gBRCA-mutated cancer is unknown. This highlights the need identify functional biomarkers...
Purpose AKT1 E17K mutations are oncogenic and occur in many cancers at a low prevalence. We performed multihistology basket study of AZD5363, an ATP-competitive pan-AKT kinase inhibitor, to determine the preliminary activity AKT inhibition AKT-mutant cancers. Patients Methods Fifty-eight patients with advanced solid tumors were treated. The primary end point was safety; secondary points progression-free survival (PFS) response according Response Evaluation Criteria Solid Tumors (RECIST)....
Abstract The utility of circulating tumor DNA (ctDNA) as a biomarker in patients with advanced cancers receiving immunotherapy is uncertain. We therefore analyzed pretreatment (n = 978) and on-treatment 171) ctDNA samples across 16 advanced-stage types from three phase I/II trials durvalumab (± the anti-CTLA4 therapy tremelimumab). Higher variant allele frequencies (VAF) were associated poorer overall survival (OS) other known prognostic factors, but not objective response, suggesting role...