New compound shows promise in treating multiple human cancers

Australian cancer researchersA collaborative team of researchers has shown that a new compound blocks a protein that is essential for the sustained growth of up to a quarter of all cancers.

The study presents a new way to efficiently kill cancerous cells and holds promise for the treatment of blood cancers such as acute myeloid leukaemia, lymphoma and multiple myeloma, as well as solid cancers such as melanoma and cancers of the lung and breast.

The new compound, S63845, targets a protein of the BCL2 family, called MCL1, which is essential for the sustained survival of cancer cells.

Associate Professor Guillaume Lessene at Walter and Eliza Hall Institute in Melbourne said the work provided the first clear preclinical evidence that inhibiting MCL1 was effective in targeting several cancer types.

“MCL1 is important for many cancers because it is a pro-survival protein that allows the cancerous cells to evade the process of programmed cell death that normally removes cancer cells from the body,” Associate Professor Lessene said.

“Extensive studies performed in a variety of cancer models have shown that S63845 potently targets cancer cells dependent on MCL1 for their survival.”

The researchers demonstrated that not only was S63845 effective against several cancer types, but that it could also be delivered at doses that were well tolerated by normal cells.

Associate Professor Lessene said the research also provided further evidence of the usefulness of a new class of anti-cancer drugs called BH3 mimetics.

“BH3 mimetics inhibit a group of proteins known as the ‘pro-survival BCL-2 proteins’,” he said.

“MCL1 is a member of this protein family, and inhibiting it activates the process of programmed cell death.”

“Walter and Eliza Hall Institute researchers revealed the role of BCL-2 in cancer more than 28 years ago and the essential role of MCL1 for the survival of malignant cells four years ago,” he concluded.

The research was supported through a research collaboration with Servier and through funding from Australian Cancer Research Foundation, the National Health and Medical Research Council of Australia, the Leukemia and Lymphoma Society (US), Cancer Council Victoria, the Kay Kendall Leukemia Fund, Victorian Cancer Agency, the Victorian Government Operational Infrastructure Scheme and the estate of Anthony Redstone.

The research was published last week online in the journal Nature.

The original news post and video were published on the WEHI website.