AGCF researcher has received a $1.1 million grant to investigate new therapy combinations for women with ovarian cancer.
The AGCF’s first research fellow, Dr Dane Cheasley, has been awarded a four-year grant from the Federal Government’s Medical Research Future Fund (MRFF) to investigate new combination therapies for a rare form of ovarian cancer.
The Peter MacCallum Cancer Centre researcher will perform this research in collaboration with Peter Mac group leader A/Prof Kaylene Simpson. Together they will use high throughput drug screening to fast-track the discovery of therapeutic combinations for the treatment of low-grade serous ovarian cancer (LGSOC).
AGCF Director, Prof Neville Hacker, himself a co-investigator on the grant, said: “These tumours are an uncommon but distinctive subtype of ovarian cancer. They frequently present with advanced disease, but they are generally resistant to chemotherapy, which makes their treatment exceptionally challenging,”
Study lead investigator, Dr Cheasley, said: “As cancer treatment becomes increasingly personalised, there is growing emphasis on drugs that target specific cancer-causing genetic aberrations. However, these drugs have shown little response as single agents so far in patients with this disease. Indeed, our comprehensive genetic study of the largest cohort of patients with low-grade serous cancers, which was funded by the AGCF, revealed that these cancers are genetically diverse. As a result, there is inevitably a small population of cells within each tumour that is resistant to any single drug treatment”
Dr Cheasley went on to say: ”While a single drug is unlikely to eradicate this cancer, combinations of drugs, targeting multiple genetic aberrations, will offer a higher chance of long-term efficacy, and hopefully even cure. Empirically identifying such drug combinations in the clinic is quite impractical, given the many possible combinations and the rarity of this disease. Hence, a sophisticated, high-throughput pre-clinical approach is required.”
This research project will use state-of-the-art robotics available at the Victorian Centre for Functional Genomics, led by A/Prof Kaylene Simpson. It will test close to 2000 clinically available drugs in combination across a large collection of patient-derived LGSOC cell lines.
Once effective therapeutic combinations have been discovered on cell lines, clinical trials will begin. Newly diagnosed patients will be recruited, and their cancer tested to determine if a particular treatment combination, based on the genetic make-up of their tumour, is likely to be effective.
“This study, which will rapidly test each individual patient’s cancer to determine the best possible therapeutic combination, should provide clinicians with a rational treatment option for each patient with low-grade serous ovarian cancer. We are very optimistic that it will improve patient outcomes in this understudied and poor prognostic group of women” said Prof Hacker.
Ms Loraine Peck, another AGCF Director, is the consumer representative on the grant. Ms Peck is herself a survivor of low grade serous ovarian cancer, and her involvement will be critical to communicating this research to the broader population.
Dr Cheasley said “The success of this grant would not have been possible without the amazing genetic data which we generated from my Australian Gynaecological Cancer Foundation grant. This work highlighted many genetic abnormalities that can be targeted by anti-cancer therapies which have been already approved for use in other cancers. Importantly, my AGCF fellowship gave me the opportunity to present my research at leading gynaecological cancer conferences in Australia and overseas. This greatly expanded my national and international network and my standing in the field of rare-ovarian cancer research, without which my MRFF success would not have been possible.”
Professor Hacker said: “Dane’s persistent dedication to pursuing a genomically directed drug discovery approach, particularly with the less common ovarian cancers, will undoubtedly be a major contribution to the field.”