Joy Hendley
A5052647168- Ovarian cancer diagnosis and treatment
- PARP inhibition in cancer therapy
- Cancer Genomics and Diagnostics
- CRISPR and Genetic Engineering
- RNA modifications and cancer
- Virus-based gene therapy research
- Cancer-related Molecular Pathways
- DNA Repair Mechanisms
- Renal cell carcinoma treatment
- Cancer-related molecular mechanisms research
- Microtubule and mitosis dynamics
- Ferroptosis and cancer prognosis
- Cancer Mechanisms and Therapy
- RNA and protein synthesis mechanisms
- Ubiquitin and proteasome pathways
- Protein Degradation and Inhibitors
- Cancer Immunotherapy and Biomarkers
- Immune Cell Function and Interaction
- Immune cells in cancer
- Animal Virus Infections Studies
- Plant Virus Research Studies
- Galectins and Cancer Biology
- Viral-associated cancers and disorders
- Cytomegalovirus and herpesvirus research
- Endoplasmic Reticulum Stress and Disease
The University of Melbourne
2012-2024
Peter MacCallum Cancer Centre
2012-2024
Monash University
2023
Hudson Institute of Medical Research
2023
Cedars-Sinai Medical Center
2022
Garvan Institute of Medical Research
2018
UNSW Sydney
2018
Royal Women's Hospital
2015
Wellcome Sanger Institute
2012
Westmead Institute
2012
Abstract Accurately identifying patients with high-grade serous ovarian carcinoma (HGSOC) who respond to poly(ADP-ribose) polymerase inhibitor (PARPi) therapy is of great clinical importance. Here we show that quantitative BRCA1 methylation analysis provides new insight into PARPi response in preclinical models and cancer patients. The 12 HGSOC patient-derived xenografts (PDX) the rucaparib was assessed, variable dose-dependent responses observed chemo-naive BRCA1/2 -mutated PDX, no PDX...
Abstract ABCB1 encodes Multidrug Resistance protein (MDR1), an ATP-binding cassette member involved in the cellular efflux of chemotherapeutic drugs. Here we report that ovarian and breast samples from chemotherapy treated patients are positive for multiple transcriptional fusions involving , placing it under control a strong promoter while leaving its open reading frame intact. We identified 15 different fusion partners as well with distinct events. The partner gene selected depended on...
Abstract Mucinous ovarian carcinoma (MOC) is a unique subtype of cancer with an uncertain etiology, including whether it genuinely arises at the ovary or metastatic disease from other organs. In addition, molecular drivers invasive progression, high-grade and are poorly defined. We perform genetic analysis MOC across all histological grades, benign borderline mucinous tumors, compare these to tumors potential extra-ovarian sites origin. Here we show that distinct supports progressive model...
Abstract High-grade serous cancer (HGSC), the most common subtype of ovarian cancer, often becomes resistant to chemotherapy, leading poor patient outcomes. Intratumoral heterogeneity occurs in nearly all solid cancers, including contributing development resistance mechanisms. In this study, we examined spatial and temporal genomic variation HGSC using high-resolution single-nucleotide polymorphism arrays. Multiple metastatic lesions from individual patients were analyzed along with 22...
Abstract Purpose: Women with epithelial ovarian cancer generally have a poor prognosis; however, subset of patients has an unexpected dramatic and durable response to treatment. We sought identify clinical, pathological, molecular determinants exceptional survival in women high-grade serous (HGSC), disease associated the majority deaths. Experimental Design: evaluated histories 2,283 and, after applying stringent clinical pathological selection criteria, identified 96 HGSC that represented...
Abstract We aimed to validate the prognostic association of p16 expression in ovarian high‐grade serous carcinomas (HGSC) and explore it other carcinoma histotypes. protein was assessed by clinical‐grade immunohistochemistry 6525 including 4334 HGSC using tissue microarrays from 24 studies participating Ovarian Tumor Tissue Analysis consortium. patterns were interpreted as abnormal (either overexpression referred block or absence) normal (heterogeneous). CDKN2A (which encodes p16) mRNA also...
Low-grade serous ovarian carcinomas (LGSC) are associated with a poor response to chemotherapy and molecularly characterized by RAS pathway activation. Using exome whole genome sequencing, we identified recurrent mutations in the protein translational regulator EIF1AX NF1, USP9X, KRAS, BRAF, NRAS were mutually exclusive; however, found significant co-occurrence of Missense clustered at N-terminus region its role ensuring initiation fidelity. Coexpression mutant proteins promoted...
Mucinous ovarian carcinoma (MOC) is an uncommon cancer histotype that responds poorly to conventional chemotherapy regimens. Although long overall survival outcomes can occur with early detection and optimal surgical resection, recurrent advanced disease are associated extremely poor survival. There no current guidelines specifically for the systemic management of MOC. We analyzed data from a large cohort women MOC evaluate potential clinical utility range agents.We gene copy number (n =...
Abstract Purpose: Gene expression–based molecular subtypes of high-grade serous tubo-ovarian cancer (HGSOC), demonstrated across multiple studies, may provide improved stratification for molecularly targeted trials. However, evaluation clinical utility has been hindered by nonstandardized methods, which are not applicable in a setting. We sought to generate grade minimal gene set assay classification individual tumor specimens into HGSOC and confirm previously reported subtype-associated...
Cyclin D1 binds and regulates the activity of cyclin-dependent kinases (CDKs) 4 6. Phosphorylation retinoblastoma protein by cyclin D1·CDK4/6 complexes during G<sub>1</sub> phase cell cycle promotes entry into S phase. is ubiquitinated degraded 26 proteasome. Previous studies have demonstrated that ubiquitination dependent on its phosphorylation glycogen synthase kinase 3β (GSK-3β) threonine 286 this event greatly enhanced binding to CDK4 (Diehl, J. A., Cheng, M. G., Roussel, F., Sherr, C....
Abstract Purpose: Although ovarian clear cell carcinomas (OCCC) are commonly resistant to platinum-based chemotherapy, good clinical outcomes observed in a subset of patients. The explanation for this is unknown but may be due misclassification high-grade serous cancer (HGSOC) as OCCC or mixed histology. Experimental Design: To discover potential biomarkers survival benefit following we ascertained cohort 68 Japanese and Australian patients whom progression-free (PFS) overall (OS) could...
Abstract Background Cyclin E1 (CCNE1) is a potential predictive marker and therapeutic target in tubo‐ovarian high‐grade serous carcinoma (HGSC). Smaller studies have revealed unfavorable associations for CCNE1 amplification overexpression with survival, but to date no large‐scale, histotype‐specific validation has been performed. The hypothesis was that high‐level of overexpression, as well combination the two, are linked shorter overall survival HGSC. Methods Within Ovarian Tumor Tissue...
Abstract Our objective was to test whether p53 expression status is associated with survival for women diagnosed the most common ovarian carcinoma histotypes (high‐grade serous [HGSC], endometrioid [EC], and clear cell [CCC]) using a large multi‐institutional cohort from Ovarian Tumor Tissue Analysis (OTTA) consortium. assessed on 6,678 cases represented tissue microarrays 25 participating OTTA study sites previously validated immunohistochemical (IHC) assay as surrogate presence functional...
Abstract Purpose: The purpose of this study was to evaluate RB1 expression and survival across ovarian carcinoma histotypes how co-occurrence BRCA1 or BRCA2 (BRCA) alterations loss influences in tubo-ovarian high-grade serous (HGSC). Experimental Design: protein classified by immunohistochemistry carcinomas 7,436 patients from the Ovarian Tumor Tissue Analysis consortium. We examined germline BRCA status a subset 1,134 HGSC, related genotype overall (OS), tumor-infiltrating CD8+ lymphocytes,...
The mechanism by which all<i>-trans</i>retinoic acid (ATRA) leads to a G<sub>1</sub> arrest of the cell cycle remains unclear. We show here that decrease in D-type cyclin levels observed following ATRA treatment correlates with an increase rate D1 ubiquitylation both T-47D and MCF-7 breast cancer lines. However, cells are more resistant than indicating degradation is not sufficient for ATRA-mediated arrest. found striking difference between these while induces elevation cdk inhibitor p27...
Abstract Whole genome duplication is frequently observed in cancer, and its prevalence our prior analysis of end-stage, homologous recombination deficient high grade serous ovarian cancer (almost 80% samples) supports the notion that whole provides a fitness advantage under selection pressure therapy. Here, we therefore aim to identify potential therapeutic vulnerabilities primary with by assessing differentially expressed genes pathways 79 samples. We observe MHC-II expression lowest tumors...