Understanding Adverse and Exceptional Outcomes in Ovarian Cancer

Grant number: 1186505 | Funding period: 2020 - 2023

Completed

Abstract

Most women with high-grade serous ovarian cancer (HGSC) die within five years of diagnosis, as tumours often develop chemotherapy resistance. However some patients have dramatic responses to chemotherapy and survive long-term. We will examine unique cohorts of Australian women with HGSC and analyse their tumour samples to uncover mechanisms underlying unexpected clinical responses, and use cell models to understand how genetic vulnerabilities can be exploited in the treatment of HGSC.

Related publications (15)

Clinicopathologic and molecular predictors of survival in BRCA-deficient tubo-ovarian high-grade serous carcinoma.

Tibor A Zwimpfer, Sian Fereday, Ahwan Pandey, Dinuka Ariyaratne, Madawa W Jayawardana, Laura Twomey, Céline M Laumont, Catherine J Kennedy, Adelyn Bolithon, Nicola S Meagher, Katy Milne, Phineas Hamilton, Jennifer Alsop, Antonis C Antoniou, George Au-Yeung, Matthias W Beckmann, Amy Berrington de Gonzalez, Christiani Bisinotto, Freya Blome, Clara Bodelon

2026-04-01

BRCA-associated homologous recombination deficiency (HRD) is present in ~50% of high-grade serous carcinomas (HGSC) and predicts s..

Real-world comparative outcomes of neoadjuvant chemotherapy with interval cytoreductive surgery versus primary cytoreductive surgery in epithelial ovarian cancer: insights from the australian ovarian cancer study (AOCS)

Tibor A Zwimpfer, Dinuka Ariyaratne, Sian Fereday, Nadia Traficante, Catherine J Kennedy, Kathryn Alsop, George Au-Yeung, Michael Friedlander, Anna Defazio, David DL Bowtell, Dale W Garsed

2026-02-01

Oxford Classic–Defined EMT Risk Stratification of High-Grade Serous Ovarian Cancer for Guiding Treatment Decisions

L Rai, A Ravaggi, E Bignotti, RL Hollis, DW Garsed, A Pandey, KB Papalois, F Patel, Y Kamel, L Campo, A Easton, J Nulsen, B Roskams-Hieter, M Artibani, L Wang, N Hussain, L Wang, N Zaarour, A Aggarwal, A Ahmed-Ebbiary

2026-01-01

Purpose: The association between epithelial-to-mesenchymal transition (EMT) in high-grade serous ovarian cancer (HGSOC) and poor p..

Overcoming intra-tumoral heterogeneity for biomarker discovery in the high-grade serous ovarian cancer proteome

SS Manda, MM Espersen, C Mapagu, N Bouantoun, J Boros, YE Chiew, S Srirangan, S Pattnaik, CJ Kennedy, AH Brand, DW Garsed, A Pandey, DDL Bowtell, N Lucas, D Xavier, S Mahboob, D Bucio-Noble, B Tully, PG Hains, PJ Robinson

2025-12-01

Improved biomarkers of treatment response are needed for patients with high-grade serous ovarian cancer (HGSC). A challenge is sub..

Exome sequencing identifies HELB as a novel susceptibility gene for non-mucinous, non-high-grade-serous epithelial ovarian cancer

EM Dicks, JP Tyrer, S Ezquina, M Jones, J Baierl, PC Peng, M Diaz, E Goode, SJ Winham, T Dörk, TV Gorp, AD Fazio, DDL Bowtell, DW Garsed, K Odunsi, K Moysich, M Pavanello, F Fostira, PM Webb, J Soukupová

2025-03-01

Rare, germline loss-of-function variants in a handful of DNA repair genes are associated with epithelial ovarian cancer. The aim o..

Immunological and molecular features of the tumor microenvironment of long-term survivors of ovarian cancer

BH Nelson, P Hamilton, MT Phung, K Milne, B Harris, S Thornton, D Stevens, S Kalaria, K Singh, CM Laumont, E Moss, A Alimujiang, NS Meagher, A Bolithon, S Fereday, CJ Kennedy, J Hendley, D Ariyaratne, K Alsop, N Traficante

2024-12-16

BACKGROUND. Despite an overall poor prognosis, about 15% of patients with advanced-stage tubo-ovarian high-grade serous carcinoma ..

Proteogenomic analysis of enriched HGSOC tumor epithelium identifies prognostic signatures and therapeutic vulnerabilities

NW Bateman, T Abulez, AR Soltis, A McPherson, S Choi, DW Garsed, A Pandey, C Tian, BL Hood, KA Conrads, PN Teng, J Oliver, G Gist, D Mitchell, TJ Litzi, CM Tarney, BA Crothers, P Mhawech-Fauceglia, CL Dalgard, MD Wilkerson

2024-12-01

We performed a deep proteogenomic analysis of bulk tumor and laser microdissection enriched tumor cell populations from high-grade..

Concurrent RB1 Loss and BRCA Deficiency Predicts Enhanced Immunologic Response and Long-term Survival in Tubo-ovarian High-grade Serous Carcinoma

FAM Saner, K Takahashi, T Budden, A Pandey, D Ariyaratne, TA Zwimpfer, NS Meagher, S Fereday, L Twomey, KI Pishas, T Hoang, A Bolithon, N Traficante, K Alsop, EL Christie, EY Kang, GS Nelson, P Ghatage, CH Lee, MJ Riggan

2024-08-15

Purpose: The purpose of this study was to evaluate RB1 expression and survival across ovarian carcinoma histotypes and how co-occu..

Homologous recombination proficient subtypes of high-grade serous ovarian cancer: treatment options for a poor prognosis group

N Stiegeler, DW Garsed, G Au-Yeung, DDL Bowtell, V Heinzelmann-Schwarz, TA Zwimpfer

2024-01-01

Approximately 50% of tubo-ovarian high-grade serous carcinomas (HGSCs) have functional homologous recombination-mediated (HR) DNA ..

Concurrent RB1 loss and BRCA-deficiency predicts enhanced immunological response and long-term survival in tubo-ovarian high-grade serous carcinoma.

Flurina AM Saner, Kazuaki Takahashi, Timothy Budden, Ahwan Pandey, Dinuka Ariyaratne, Tibor A Zwimpfer, Nicola S Meagher, Sian Fereday, Laura Twomey, Kathleen I Pishas, Therese Hoang, Adelyn Bolithon, Nadia Traficante, Kathryn Alsop, Elizabeth L Christie, Eun-Young Kang, Gregg S Nelson, Prafull Ghatage, Cheng-Han Lee, Marjorie J Riggan

2023-11-10

BACKGROUND: Somatic loss of the tumour suppressor RB1 is a common event in tubo-ovarian high-grade serous carcinoma (HGSC), which ..

The Prognostic Effect of Immune Cell Infiltration Depends on Molecular Subtype in Endometrioid Ovarian Carcinomas

Karolin Heinze, Evan S Cairns, Shelby Thornton, Bronwyn Harris, Katy Milne, Marcel Grube, Charlotte Meyer, Anthony N Karnezis, Sian Fereday, Dale W Garsed, Samuel CY Leung, Derek S Chiu, Malak Moubarak, Philipp Harter, Florian Heitz, Jessica N Mcalpine, Anna Defazio, David DL Bowtell, Ellen L Goode, Malcolm Pike

2023-09-01

Purpose: Endometrioid ovarian carcinoma (ENOC) is the second most-common type of ovarian carcinoma, comprising 10%-20% of cases. R..

Multiomic analysis of homologous recombination-deficient end-stage high-grade serous ovarian cancer

NL Burdett, MO Willis, K Alsop, AL Hunt, A Pandey, PT Hamilton, T Abulez, X Liu, T Hoang, S Craig, S Fereday, J Hendley, DW Garsed, K Milne, S Kalaria, A Marshall, BL Hood, KN Wilson, KA Conrads, KI Pishas

2023-03-01

High-grade serous ovarian cancer (HGSC) is frequently characterized by homologous recombination (HR) DNA repair deficiency and, wh..

Profiling the immune landscape in mucinous ovarian carcinoma

NS Meagher, P Hamilton, K Milne, S Thornton, B Harris, A Weir, J Alsop, C Bisinoto, JD Brenton, A Brooks-Wilson, DS Chiu, KL Cushing-Haugen, S Fereday, DW Garsed, SA Gayther, A Gentry-Maharaj, B Gilks, M Jimenez-Linan, CJ Kennedy, ND Le

2023-01-01

Objective: Mucinous ovarian carcinoma (MOC) is a rare histotype of ovarian cancer, with low response rates to standard chemotherap..

Beating the odds: molecular characteristics of long-term survivors of ovarian cancer

Dale W Garsed, David DL Bowtell

2022-12-01

High-grade serous ovarian cancer, the most common form of the disease, is often fatal. This study investigated the genomic and imm..

The genomic and immune landscape of long-term survivors of high-grade serous ovarian cancer

DW Garsed, A Pandey, S Fereday, CJ Kennedy, K Takahashi, K Alsop, PT Hamilton, J Hendley, YE Chiew, N Traficante, P Provan, D Ariyaratne, G Au-Yeung, NW Bateman, L Bowes, A Brand, EL Christie, JM Cunningham, M Friedlander, B Grout

2022-12-01

Fewer than half of all patients with advanced-stage high-grade serous ovarian cancers (HGSCs) survive more than five years after d..

University of Melbourne Researchers

Dale Garsed