Dr Liz Christie, a specialist in treatment resistance in ovarian and endometrial cancer at Peter Mac, said her findings, published today in Nature Genetics, will help develop new treatments for ovarian cancer which impacts 1800 Australians each year.
“We used a combination of genomic sequencing, targeted DNA sequencing, and applied immune and proteomic profiling to uncover that each patient had tumours that became resistant to treatment in multiple ways,” Dr Christie said.
“Our study, in collaboration with researchers in Canada and the USA, found that one mechanism was causing the cancer cells to resist treatment in nearly 50 per cent of patients.
“However, while one mechanism was causing the cells to resist treatment in almost half of the patients, as many as nine different factors were influencing this resistance.
“Uncovering the process that causes treatment resistance in ovarian cancer allows us to focus on finding new therapies that target these resistance mechanisms early and improve outcomes for patients.
“We also identified that in many patients the cancers had developed multiple mechanisms to resist treatment,” she said.
The study involved Peter Mac’s pioneering CASCADE program, which enrols patients with advanced metastatic disease who consent to undergo rapid autopsy following death to aid research efforts.
“In a world-first, Dr Christie and Dr Nikki Burdett from Peter Mac evaluated a large number of autopsy samples from high grade serous ovarian cancer patients with a BRCA1/2 mutation,” said Professor David Bowtell, Group Leader at Peter Mac and CASCADE program lead.
“Traditionally these patients have a poor prognosis and acquired resistance to treatment is common.”
“This new discovery provides us with a clear focus for new therapies that can evade the way cancer cells develop resistance to treatment,” he said.
The new paper ‘Multiomic analysis of homologous recombination-deficient end-stage high grade serous ovarian cancer’ has been published in Nature Genetics.