The study – presented as a ‘late-breaking abstract’ at the American Society of Hematology in San Diego and published in the journal Cancer Discovery – was a collaborative effort between the Walter and Eliza Hall Institute, Peter MacCallum Cancer Centre, Royal Melbourne Hospital and the University of Melbourne.
The Institute’s Professor David Huang who co-led the research said the team found a unique genetic mutation in the leukaemia cells of seven patients who relapsed while taking venetoclax.
“The mutation was found in BCL2 which is the survival protein targeted by venetoclax. This explained why the drug wasn’t effective in these patients.”
Professor Andrew Roberts who is head of clinical translation at the Institute and a haematologist at the Royal Melbourne Hospital and Peter MacCallum Cancer Centre said venetoclax remained a very effective treatment for CLL and the findings would help to further enhance the therapy for patients at risk of relapse.
“This important clue should help us develop combination treatments with venetoclax that are even better for people with CLL.”
Professor Huang said the work was an excellent example of teamwork and a multidisciplinary approach to successful research translation.
“Combining clinical skills with ones in cancer genomics, biology and biochemistry, the team worked rapidly to pinpoint and characterise the mutation,” he said.
“Haematologist and Institute clinician scientist Dr Mary Ann Anderson identified many of the appropriate patients for the study and managed their involvement; Dr Piers Blombery from the Peter Mac undertook the genomic assessment of cancer cells from relapsed patients; and our terrific post-doctoral fellows Dr Jianan Gong, Dr Rachel Thijssen and Dr Richard Birkinshaw undertook the laboratory research that explained why the mutation caused venetoclax resistance,” he said.
Dr Rachel Thijssen whose expertise in cancer biology helped to prove that leukemic cells with the mutation were resistant to venetoclax said she was delighted to be a part of the team and contribute to the study.
“I came to the Institute to study why some patients do not respond to venetoclax and being a joint first author on this paper is a great outcome.
“We are now working together with our colleagues in the precinct to develop ways to overcome venetoclax resistance in CLL patients,” she said.
The research was supported by the Snowdome Foundation, the Christine and Bruce Wilson Centre for Lymphoma Genomics, the Leukemia and Lymphoma Society (USA), the Leukaemia Foundation, Australian Cancer Research Foundation, Cancer Council Victoria, the Victorian Comprehensive Cancer Centre, the National Health and Medical Research Council and the Victorian Government.
Venetoclax is the result of a research collaboration between the Institute and companies Genentech, a member of the Roche Group, and AbbVie. The potent anti-cancer drug, co-developed and trialled in Australia, was based on a landmark research discovery made at the Institute in the late 1980s, that a protein called BCL2 helps cancer cells survive indefinitely.
The Walter and Eliza Hall Institute is a member of the Victorian Comprehensive Cancer Centre (VCCC) alliance. The VCCC is a collaborative network of Victorian hospitals and research centres improving the prevention, diagnosis and treatment of cancer.
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