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Targeting cancer ‘survival’ protein to kill cancer cells

A protein critical for the survival of many cancer cells, called MCL-1, might be the key to a new treatment for lymphoma and leukaemia patients.

Dr Stephanie Grabow. Photo courtesy of the Walter and Eliza Hall Institute of Medical Research.
Dr Stephanie Grabow. Photo courtesy of the Walter and Eliza Hall Institute of Medical Research.

Leukaemia Foundation funded researcher Dr Stephanie Grabow and her team, in particular Drs Gemma Kelly and Brandon Aubrey at Melbourne’s Walter and Eliza Hall Institute of Medical Research, are investigating the role of  MCL-1 and testing new drugs that target MCL-1 in pre-clinical models of lymphoma.

Dr Grabow’s research is based on a lymphoma model that is driven by the oncogene MYC, which when deregulated frequently causes cancer in humans.  Her work has broad impact on cancer therapy since around 70% of human cancers, including many leukaemias and lymphomas, have deregulated MYC.

The question Dr Grabow and colleagues are trying to answer is whether the protein MCL-1 is required for the survival of MYC-driven cells that develop into lymphoma (and possibly other MYC-driven cancer) cells.

MCL-1 protein is also important for many normal cells

The team recently found that many cancer cells relied on the MCL-1 protein to live and could not survive without this protein. This ground-breaking research was part-funded by the Leukaemia Foundation.

MCL-1 is a promising target for the development of a new drug that could disable the protein and kill the cancer cell. However, since many normal healthy cells also depend on MCL-1, researchers are now analysing the amount of MCL-1 protein required for the development and continued growth of leukaemia, lymphoma and other cancers, and comparing this to the extent of MCL-1 reduction that normal tissues can tolerate without damage.

This knowledge is needed to develop treatment regimen for cancer therapy that will be safe.

Leukaemia Foundation funds advance research

Dr Grabow was this year awarded a $200,000 Leukaemia Foundation Postdoctoral Fellowship (2015-16) to carry out this research, with her colleague Margs Brennan receiving a $120,000 PhD scholarship (2015-17) for her work on MCL-1.

“The data I gather will help us understand what amount of MCL-1 protein we need to inhibit to effectively kill leukaemia and lymphoma cells without causing adverse side-effects through killing of important normal cells,” Dr Grabow said.

“We have highly promising preliminary results on MCL-1 in laboratory models of human lymphomas and leukaemias,” she said.

Dr Grabow is also looking at whether other cell survival proteins may substitute for MCL-1 to help the cancer cells adjust to a reduction in MCL-1. If this is the case, a combination of cell survival proteins may have to be targeted by drugs to achieve the most efficient therapeutic effect.

Another component of Dr Grabow’s research is to identify gene mutations commonly found in leukaemias and lymphomas that correlate with high dependency on MCL-1 for survival. This will help identify diagnostic biomarkers to identify those lymphomas and leukaemias that will benefit the most from drugs that inhibit MCL-1.

Dr Grabow hopes that MCL-1 inhibitors will improve treatment strategies and outcomes for lymphoma and leukaemia patients.

In this short film courtesy of  Walter and Eliza Hall Institute of Medical Research, Dr Gemma Kelly and Professor Andreas Strasser outline the important work the team is doing:

Last updated on February 23rd, 2022

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