Peter Mac researchers have been awarded a four year grant from the Federal Government’s Medical Research Future Fund to investigate new combination therapies for a rare form of ovarian cancer.

The research, led by Peter Mac’s Dr Dane Cheasley in collaboration with A/Prof Kaylene Simpson and the University of New South Wales’ Prof Neville Hacker, will use high throughput screening to fast-track the discovery of therapy combinations for the treatment of low-grade serous ovarian cancer (LGSOC).

LGSOC represent about 5% of all epithelial ovarian cancers. While the term ‘low-grade’ suggests the disease is low risk, advanced LGSOC carries a poor prognosis, and women with LGSOC who have residual disease after surgery have an overall survival rate of just 15% at 5 years.

Further, LGSOC are largely unresponsive to standard ovarian cancer chemotherapy, meaning alternative treatment strategies for LGSOC are urgently needed.

Study lead investigator, Dr Cheasley, says that a combined approach to treatment could be the key to better outcomes for women with LGSOC.

“While a single drug is unlikely to be sufficient to completely eradicate some LGSOC’s, combinations of drugs targeting multiple mutations and cancer pathways could offer a higher chance of long-term efficacy and even cure,” explains Dr Cheasley.

“Our research will explore just this. We will rationally select anti-cancer therapies already approved for use in people and known to specifically target mutations driving the growth of LGSOC cells.

“We will then use state-of-the-art facilities at the Victorian Centre for Functional Genomics (VCFG) at Peter Mac to conduct high-throughput screening of thousands of drug combinations against 20 cell lines capturing the molecular diversity of the disease.”

A/Prof Simpson, Head of the VCFG and co-investigator on the study says that high-throughput technologies, such as those being used in this work, are the key to fast-tracking the discovery of important drug combinations that can carve months, or even years, off the drug discovery process.

“Empirically identifying drug combinations in the clinic - a traditional approach used with chemotherapy development - is simply impractical given the many agents and combinations that could be explored, and the rarity of LGSOC,” says A/Prof Simpson.

“By using high-throughput screening technologies we can overcome these limitations, speeding up the discovery process and helping to quickly translate these findings into better treatments for people with cancer.”

Once effective therapy combinations have been discovered on cell lines, researchers will test whether they also work to kill cancer cells taken directly from women with LGSOC, and identify biomarkers that predict whether a cancer will respond to the treatments.

“This innovative project is the first of its kind for LGSOC and will create immediate clinical drug development opportunities. Application of drug combination therapy is the best approach to lower treatment failure rate and to significantly improve LGSOC patient outcomes,” says Dr Cheasley.