Scientists studying a neglected tropical disease have made a chance discovery—a promising therapeutic target for a deadly blood cancer. Institut Pasteur and Inserm researchers were investigating Buruli ulcers: infectious open sores caused by Mycobacterium ulcerans, a pathogen from the family of bacteria that cause leprosy and tuberculosis.
Buruli ulcers are a form of skin necrosis triggered by a toxin called mycolactone that the bacteria secrete. In previous studies, the scientists found that mycolactone affects the endoplasmic reticulum, a cell organelle that plays various roles, including producing hormones and lipids. The toxin blocks the function of the endoplasmic reticulum, ultimately resulting in the buildup of proteins inside the cell, causing it to self-destruct.
Interestingly, in their latest work, the researchers show that mycolactone is also incredibly lethal towards multiple myeloma cells, a cancer of mature plasma cells in the bone marrow. The researchers demonstrate that the toxin can kill tumor cells in animal models and tumor samples from patient biopsies. Most promisingly, mycolactone is harmless to healthy cells and is highly toxic to multiple myeloma cells that have become resistant to existing cancer therapies.
Factors such as radiation exposure and family history can contribute to an elevated risk of multiple myeloma, although the exact causes of the cancer are still unknown. The cancer is treated with steroids, stem cell transplants, or a class of chemotherapies known as proteasome inhibitors. While these therapies work well initially—particularly in patients at the early stages of the disease—over time, patients tend to become resistant to the treatment, and the cancer relapses.
The discovery of mycolactone’s powerful, selective effects on multiple myeloma cells paves the way for next-generation therapies with the potential to keep tumors in remission for longer, or possibly even permanently.