Stephanie Grabow, Liz Valente,
and Andreas Strasser
Photo courtesy of the
Walter and Eliza Hall Insitute
Targeting a cell survival protein could overcome treatment resistance in T-cell lymphomas, according to preclinical research published in Blood.
Investigators found that removing the pro-survival protein MCL-1 prompted the death of lymphoma cells that had become resistant to conventional treatments.
The team noted that half of all cancers become resistant to chemotherapy and radiotherapy by acquiring mutations in the tumor-suppressing p53 protein.
And their research showed that MCL-1 helps these cancer cells survive by subverting the normal process of apoptosis.
“There are several pro-survival proteins that promote the sustained survival of cancer cells; the challenge is to identify which one is the most important in keeping each type of cancer cell alive,” said Stephanie Grabow, PhD, of the Walter and Eliza Hall Institute of Medical Research in Victoria, Australia.
“When we removed MCL-1 in models of T-cell lymphoma that had ‘lost’ the tumor-suppressing protein p53, cancers could not develop, demonstrating that MCL-1 is critical for the development of T-cell lymphomas.”
“Previous work from our colleagues at the institute has shown that MCL-1 is also critical for the survival and therapy-resistance of other blood cancers, including B-cell lymphoma and acute myeloid leukemia, indicating that is a very important target for potential new anticancer treatments.”
So the new finding reinforces the need to develop compounds that specifically target MCL-1, said Andreas Strasser, PhD, also of the Walter and Eliza Hall Institute.
“Investigating the role of MCL-1 and other proteins involved in controlling apoptosis has shown that MCL-1 is a critical protein in the survival of many types of cancer cells,” he said. “Targeting MCL-1 could therefore allow us to develop new, urgently needed therapies to treat cancers that have stopped responding to other anticancer drugs.”
Dr Grabow said the researchers will continue to investigate the role of MCL-1 in the development and progression of other cancers.
“Finding new treatment targets is crucial if we are to reduce the impact of these diseases,” she concluded.
