Protein Target Found in Drug-Resistant Lymphomas

Researchers at the Walter and Eliza Hall Institute of Medical Research in Melbourne, Australia, have discovered a protein that could help treat certain lymphomas, including those resistant to therapy.

The study was published in the 2014 November issue of Blood, a journal published by the American Society of Hematology.

Professor Andreas Strasser and colleagues, have discovered that removing the "survival" protein MCL-1, caused death and elimination of lymphoma cells that had become resistant to standard cancer treatments.

The MCL-1 protein is considered a key regulator of apoptosis, but when this process is disrupted, cancer cells have a better chance at surviving-even when exposed to harsh cancer treatments.

Cancer cells have the ability to become resistant to both chemotherapy and radiation treatment by acquiring mutations in the p53 tumor suppressor gene. According to researcher Dr. Stephanie Grabow, MCL-1 helps cancer cells survive by suppressing the normal process of apoptosis.

"When we removed MCL-1 in models of T-cell lymphoma that had ‘lost’ the tumour 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 leukaemia, indicating that is a very important target for potential new anti-cancer treatments," said Grabow.

The next step may be developing targeted therapy drugs specifically aimed at MCL-1-especially those cancers no longer responsive to existing treatments.

"When cancers acquire mutations in p53, they become resistant to many conventional therapies," said Strasser. "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. Targeting MCL-1 could therefore allow us to develop new, urgently needed therapies to treat cancers that have stopped responding to other anti-cancer drugs."

The institute's research team will continue to investigate the role of MCL-1 in other cancers as well, including blood and brain cancers.