Validation of new treatments for low-grade serous ovarian cancer

Experts on a rare subtype of ovarian cancer called low-grade serous ovarian cancer will trial promising drug combinations for treating the disease, with the view to identifying the most promising drug combination, to inform a new targeted treatment.

Project Details

Low grade serous ovarian cancer (LGSOC) doesn’t respond well to currently available therapies such as chemotherapy, so Dr Dane Cheasley is investigating new and effective treatments to boost the currently low survival rate. Previously, he’s studied the characteristics that make LGSOC unresponsive to therapy. Now, the team will test a series of drug combinations, that have shown promise in treating other cancers but have never been tested on LGSOC.

Aims:

• Demonstrate how effective each of the 20 identified drugs are against LGSOC by testing them alone, in combination with each other and alongside standard treatments including chemotherapy, in essential pre-clinical experiments.
• Assess how toxic each of the 20 drugs are to healthy cells, to eliminate those that damage healthy cells and therefore identify those least likely to cause side effects.
• Identify the most effective and least toxic drug combinations, that show promise across all subtypes of LGSOC, and across LGSOC patient samples of diverse genetic makeup, to ensure that the team can present a potential solution for all patients.

Approach:

Dr Cheasley took an encompassing approach to screening Therapeutic Goods Administration (TGA)-approved drugs to narrow down those with the most potential to be repurposed as an LGSOC treatment.

“We screened every known potential drug, rather than testing only a few promising ones.”

In previous studies he used powerful high-throughput screening technology, which allows thousands of samples to be rapidly examined, to screen 3,500 potentially suitable drugs. These had all been approved for use in treating other cancers or for phase 1 clinical trials. He tested the most promising 100 drugs in 12 LGSOC patient samples to identify the 20 most effective.

If successful, this project could produce a compelling case for a small clinical trial of approximately ten patients in a collaboration between Australian and Canadian researchers and clinicians.

Ambition and outcomes:

LGSOC is a rare ovarian cancer with scarce funding and accessible samples, making development of effective treatments a challenge. This project has the potential to change the treatment landscape for LGSOC patients in significant need. Importantly, the drug combinations will be tested on both first diagnosis LGSOC samples and samples with recurrent disease to evaluate effectiveness across both cases.

Although new drug treatments often take a long time to develop and can be expensive for patients, Dr Cheasley has focused his research on TGA approved drugs as it is more feasible to fast track them into the clinic. Additionally, the drugs are off patent and therefore more affordable. Dr Cheasley’s considered approach aims to make highly effective LGSOC treatments as accessible as possible to as many as possible, as soon as possible.

Dr Cheasley's project will commence in July 2024.

This article has been reviewed and approved by Dr Dane Cheasley.

Key Terms

Low grade serous ovarian cancer (LGSOC): a rare subtype of ovarian cancer that accounts for approximately 5-10% of all ovarian cancers.

Drug screening: the process of testing a large number of existing drugs, which may not be currently used for that particular disease. The goal of drug screening is to identify and repurpose drugs to avoid lengthy and expensive clinical trials processes.

Recurrent disease: Disease that comes back after it has initially been treated.