A new study has the potential to improve the effectiveness of PARP inhibitors using RNA technology. It may also provide a completely new drug combination treatment, which could save the lives of thousands of women and girls.
Associate Professor Stacey Edwards’ mother was diagnosed with early onset breast cancer in the 1980s. A desire to find answers for women like her mother, coupled with an innate curiosity of how the body worked, steered Stacey’s career into breast cancer research. Having witnessed meaningful research progress for breast cancer, she believes ovarian cancer patients deserve more treatment options that will give them the best chance of survival.
With funding of $495,000 awarded by the OCRF, Stacey’s project will focus on developing a new treatment strategy that will also manage recurrence for high-grade serous ovarian cancer, the most common and aggressive ovarian cancer sub-type.
The science behind Stacey’s project begins with the DNA repair pathways in the body’s cells. Day-to-day cells get damaged, and these pathways facilitate repair. However, cancer can occur if one of the main DNA repair pathways becomes faulty as cells then repair the DNA incorrectly, and can spread to other parts of the body. PARP inhibitors are a new class of drugs that can treat cancer cells that have lost one DNA repair pathway. PARP inhibitors work by stopping the function of a second DNA repair pathway. Cancer cells cannot tolerate the loss of two DNA repair pathways which leads to cancer cell death. However, the cancer often becomes resistant to PARP inhibitor drugs.
Stacey’s goal is to identify new molecules that can be used in combination with PARP inhibitors so that a multi-pronged treatment approach stops the cancer in its tracks and inhibits recurrence, in the least harmful manner for patients.
To do this the team will focus on a new type of molecule called long non-coding RNAs (IncRNAs). LncRNAs play an important role in cells by helping certain genes to turn on and off. Stacey’s team will first identify and then screen thousands of these molecules simultaneously using gene editing technology to determine which lncRNAs will work the best when used together with PARP inhibitor drugs. The team will then trial targeting the IncRNAs using a combination of PARP inhibitor and antisense oligonucleotide drugs. These drugs can specifically bind to and degrade IncRNAs within the cancer cell. This combination of PARP inhibitor and drug innovation could completely remove two or more DNA repair pathways that the cancer relies upon to grow.
If successful, this will be the first study to identify all lncRNAs involved in DNA damage pathways and assess how they function in ovarian tumours. It may also provide a completely new combination therapy strategy which could save the lives of women and girls who, with current treatment methods, have only a 46% chance of survival beyond 5 years.
The OCRF’s funding is crucial for Stacey and her team because funding is scarce for early-stage discovery projects like Stacey’s. However, if successful her results could be a game changer for ovarian cancer treatment.
Stacey’s interest in research may have begun with a desire to find answers for women like her mother. Yet Stacey has seen that research is the solution to increasing survival rates in other cancers –and her passion to discover solutions for ovarian cancer patients is enduring.
I turn up every day because I want to make a difference."
Associate Professor Stacey Edwards
The OCRF is proud to invest in multiple promising research projects to develop more effective, personalised treatments for ovarian cancer patients. Improving treatment options for women and girls in the here and now is vital to improving survival and also providing hope to these women and their families.
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