Ovarian cancer is most commonly treated with a chemotherapy drug called cisplatin. Cisplatin works by damaging DNA so much that the tumour cells die. It forms the basis of most combined treatment regimes (where two or more drugs are used in combination). The downside to cisplatin is that it is extremely toxic and although some patients benefit substantially from treatment, a large proportion suffer the toxic side effects without any therapeutic benefit.

We are aiming to develop a personal test to determine if cisplatin is likely to be effective or if an individual’s ovarian cancer has become chemoresistant, so that the toxic side effects can be avoided if the drug is not working.

Previous financial support has allowed us to measure 2 proteins in over 200 ovarian cancers where we have the information on whether or not each tumour responded to cisplatin and if it developed resistance. The results were very conclusive: after chemotherapy if the protein called ERCC1 is present, the patient is very likely to have responded well to treatment and will have long-term survival. Patients that had no detectable ERCC1 protein in their tumour tissue after chemotherapy, relapsed quickly and had very short survival times.

Ovarian cancer cells that have become chemoresistant will accumulate lots of DNA-damage from the chemotherapy but unfortunately, they continue to grow. It is well-known there are some other cancer types such as melanoma and lung cancers, that grow rapidly and have lots of DNA damage. These cancers all respond exceptionally well to new drugs called immunotherapy that ‘take the breaks off’ the immune system and let it kill the tumours.

We aim to use the ERCC1 test to determine which patients are most likely to have become chemoresistant and have lots of DNA-damage. This will also predict that the same patients will go on to respond well to immunotherapy.

The HMRI Solution:
HMRI researcher Dr Nikola Bowden is in the unique position of understanding the science of melanoma immunotherapy as well as ovarian drug therapy. She has a 5 year plan to translate findings from the laboratory to the clinic for ovarian cancer patients:

Year 1 & 2 : Preclinical Lab Data Collection to confirm using experiments that patients who respond well (long-term) to chemotherapy, have higher levels of the protein ERCC1, after chemotherapy, compared to patients who relapse, who have low levels of this protein. Build on national and international collaborations- Prof Anna de Fazio (Sydney) & Prof. Anil Sood (Texas)
Year 3: Develop a test that will tell oncologists if chemotherapy is likely to have worked, in collaboration with NSW Pathology. Commence local Phase 2 Clinical Trial based at the Calvary Mater Newcastle with Dr Janine Lombard & Dr Andre van der Westhuizen (medical oncologists).
Year 4: Expand to national Phase 2 Clinical Trial: Sydney, Melbourne, Brisbane, Perth
Year 5: Data analysis, publication and implementation in the health services.

These results will be used to develop a new combination of chemotherapy and immunotherapy clinical trial to improve treatment options for patients with advanced ovarian cancer.

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