A multiple modality approach for targeting treatment-resistant ovarian cancer

High-grade serous ovarian cancer (HGSOC) accounts for 70% of ovarian cancer (OvCa) deaths and its five-year survival rate is 43%. 50% of HGSOC demonstrate deficiencies in the homologous recombination (HR) DNA repair pathway, most commonly mutations in BRCA1/2, which underpin favourable responses to chemotherapy and Poly-(ADP-ribose) polymerase (PARP) inhibitors (PARPi). However, most women relapse within three years and succumb to chemo- and PARPi-resistant disease.

Immunotherapy has emerged as a new promising therapeutic approach in cancer care, however, the response to single immunotherapy agents in OvCa is modest (6-30%). OvCa is considered immunologically “cold” and immunosuppressed due to decreased expression of Type I interferon (IFN) genes, low level of T cell infiltration and poor response to T cell checkpoint inhibitors. This proposal addresses a significant clinical need in developing effective treatments for refractory OvCa and in applying immunotherapy to “cold” OvCa tumours.
This project aims to identify efficacious combination therapy regimens that incorporate the novel RNA polymerase I (Pol I) transcription inhibitor CX-5461 and DNA damage response inhibitors for treatment of relapsed OvCa. We aim to identify strategies that enhance anti-tumour immunity, and to design optimal combination therapies with immunotherapies to enhance anti-tumour efficacy and improve survival in ovarian cancer.

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.

https://www.petermac.org/research/labs/rick-pearson

Peter MacCallum Cancer Centre in Melbourne 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.
https://www.petermac.org/education/research-education

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.

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.
https://www.petermac.org/education/comprehensive-cancer-phd-program