Dr Emma Bolderson, from QUT's School of Biomedical Sciences, has received a $460,552 grant from the Ovarian Cancer Research Foundation (OCRF).
Dr Bolderson, a member of QUT's School of Biomedical Sciences and the Centre for Genomics and Personalised Health, will investigate a new treatment for the rare and aggressive ovarian cancer, clear-cell carcinoma (OCCC).
Dr Bolderson said this proposed treatment could stop the cancer cells being able to repair themselves and make them susceptible to anti-cancer drugs.
"OCCC accounts for around 5 - 10 per cent of ovarian cancers and are often resistant to chemotherapy and other available treatments," Dr Bolderson said.
"Usually in ovarian cancer cells that have issues repairing their DNA, drugs called PARP inhibitors (PARPi) can be extremely effective.
"However, in tumours, such as OCCC that generally have efficient DNA repair processes, the cancer cells are much more resistant to PARPi.
"To counter this, this research will focus on targeting a process that allows a cancer cell's DNA to repair itself.
"Our previous research has demonstrated that lactate is produced during OCCC cell metabolism, and during DNA repair processes, lactate is added to DNA-associated proteins called histones in a process known as lactylation."
Dr Bolderson said the research team's next steps were to:
- Determine, for the first time, the specific sites that the lactate binds to histones in OCCC cells after DNA damage occurs. "This knowledge will help us understand where in the DNA repair process a treatment would need to be targeted."
- Test the best way to stop the lactylation process to prevent the OCCC cells from repairing themselves, thereby sensitising them to DNA-damaging treatment including PARP inhibitors.
"Our team believes that when lactate gets added to the histone proteins it helps to open up the DNA to allow the cancer cells to repair themselves and so if we can develop a treatment to stop this process it could lead to cancer cells dying," she said
"Once we know where and how lactylation is occurring, we will test various treatment avenues, in combination with therapies such as PARP inhibitors to find the most effective one with the least side effects.
"One approach we will focus on is a novel therapy that combines PARP inhibitors with a novel treatment that we have designed.
"If the most promising results are found when other known inhibitors are used with PARP inhibitors, this treatment approach could potentially proceed quickly to clinical trials within the next five years as these drugs have previously undergone clinical trials and PARPi are already used to treat other ovarian cancers.
"However, if we get promising results with fewer side effects for our novel drug, we could further progress this novel therapy to benefit patients with difficult-to-treat OCCC.
"This project could also lead to improved maintenance therapies for women with OCCC to prevent recurrence."
OCRF Chief Executive Officer Robin Penty said there was an urgent need to accelerate research for women with rare ovarian cancers, including ovarian cancer clear-cell carcinoma.
"I believe we are on the cusp of change for ovarian cancer. For too long the statistics have been stubborn and progress toward effective methods of early detection, and development of enduring successful treatments, has been too slow," she said.
"Momentum, however, is building. This funding is critical in enabling researchers like Dr Bolderson to provide hope and improved outcomes for all those impacted by ovarian cancer."
- Ovarian cancer is not one disease – there are more than 30 subtypes making detection and treatment even more challenging. Standard treatments for ovarian cancer have changed little in 30+ years. Investing in research will allow for the development of more innovative treatment options that could improve survival and quality of life.
- The current five-year survival rate for ovarian cancer is 49 per cent, meaning of those diagnosed today, just half will be alive in five years' time.
- Ovarian cancer is the most lethal gynaecological cancer: investing in high-potential research is the answer to increasing the survival rate, which has barely changed in decades.
- There is no early detection test available. An effective early detection test for ovarian cancer could drastically increase the rates of early-stage diagnosis when the disease can be more effectively treated.
- A pap smear does not detect ovarian cancer, it detects human papillomavirus (HPV) which can cause cervical cancer.
