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Activation of targeted DNA Damage Response as a novel therapy for Ovarian Cancer

Project Description

High-grade serous ovarian cancer (HGSOC) is the most common and aggressive subtype of ovarian cancer and accounts for 70% of all ovarian cancer deaths. HGSOC patients are treated by surgery and/or chemotherapy, yet within 5 years most of these women relapse making new treatment options essential.

We developed a “first in class” drug, CX-5461 that activates DNA damage response, selectively kills cancer cells and is in clinical trials in haematologic (Peter Mac) and breast cancers (Canada). Importantly, our studies demonstrate substantial efficacy of CX-5461 in HGSOC, which is the basis of a new trial in ovarian cancer we are planning in 2018/19.

50% of HGSOC is characterized by defects in the homologous recombination (HR) DNA repair pathway. Aberrations in DNA repair provide a weakness that can be exploited therapeutically with genotoxic chemotherapy and inhibitors of DNA repair such as PARP inhibitors (PARPi), now approved in the clinic. Our data demonstarte that CX-5461 in combination with PARPi has significant therapeutic benefit against HGSOC patient-derived xenograft models.

This project aims to investigate the efficacy of CX-5461 in combination with chemotherapy and inhibitors of DNA repair and DNA damage response in pre-clinical models of HGSOC to facilitate clinical trials of effective combination therapies.

The Pearson laboratory investigates the molecular basis of the regulation of signalling pathways and their control of cell growth. We aim to understand how deregulation of this process contributes to cancer and how it can be targeted to treat the disease, by:

1) Understanding the signal transduction pathways underpinning cell growth control.
2) Conducting biochemical and cell biology analysis of the role of deregulated cell growth in cancer.
3) Analysing novel therapies targeting cell growth to treat cancer in pre-clinical models of lymphoma, ovarian and prostate cancers.
4) Pharmacogenomic analysis of the pathogenesis of ovarian cancer and predictors of response to emerging targeted therapies.

Peter MacCallum Cancer Centre, Melbourne Australia
Peter MacCallum Cancer Centre is Australia’s only public hospital solely dedicated to cancer, and home to the largest cancer research group in Australia. Cancer is a complex set of diseases, and modern cancer research institutes such as Peter Mac conduct research covering a diversity of topics that range from laboratory-based studies into the fundamental mechanisms of cell growth, translational studies that seek more accurate cancer diagnosis, clinical trials with novel treatments, and research aimed to improve supportive care.

All students engaged in postgraduate studies at Peter Mac are enrolled in the Comprehensive Cancer PhD (CCPhD) program, regardless of which university they are enrolled through. The program is managed by the Sir Peter MacCallum Department of Oncology (The University of Melbourne), based at Peter Mac.

Tapping into the depth and breadth of knowledge and experience offered by the ten partners of the Victorian Comprehensive Cancer Centre (VCCC) alliance, the University of Melbourne’s Comprehensive Cancer PhD Program provides a unique opportunity for multidisciplinary cancer-related PhD candidates to experience clinical and research activities across the alliance.

The Comprehensive Cancer PhD program builds on established conventional training for cancer research students providing a coordinated program of skills, research and career training in addition to usual PhD activities. The program is designed to complement existing PhD activities and provides opportunities to develop professional skills that will help candidates to fulfil their career ambitions.

Funding Notes

All PhD students at Peter Mac must have a scholarship from The University of Melbourne or through another government, trust or philanthropic organisation. Before applying for a scholarship, you must have agreed on a project with an institute supervisor.

For further information about the university application process, see:
View Website

For further information regarding scholarships (both local and international), see:
View Website
Closing dates for applications for scholarships to commence in 2019: Round 1 -31 October 2018; Round 2 - 28 Nov 2018; Round 3 - 20 Feb 2019.

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