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Multiple myeloma is a cancer caused by the abnormal proliferation of plasma cells (white blood cells that produce antibodies) in the bone marrow
.
Scientists from the Pasteur Institute and Inserm, in collaboration with the University of Paris and the Saint-Louis Hospital (AP-HP), have described a new mechanism for selectively killing these cancer cells
Researchers at the Institut Pasteur's Division of Infection Immunobiology discovered this phenomenon while studying a completely different disease: Buruli ulcer
.
This neglected tropical disease is caused by infection with a type of bacteria (Mycobacterium ulcerans) that can cause severe and irreversible skin necrosis
A transposon, a channel anchored in the wall of a cell compartment called the endoplasmic reticulum, plays a crucial role in the synthesis of a subset of proteins destined to be secreted in the extracellular medium
.
Transposons control the entry of these proteins into the endoplasmic reticulum, the main channel of the secretory pathway
Using mouse models and tumor biopsies from patients, the researchers demonstrated that bacterial lactones are highly resistant to a variety of myeloma cells, including those resistant to proteasome inhibitors, at doses that are nontoxic to normal cells.
Toxicity
.
In addition, they showed that bacteriolactone and proteasome inhibitors work synergistically to mutually enhance their anticancer effects
"This study provides proof-of-concept that the transposon is a new therapeutic target in multiple myeloma
.
The next step will be to identify drug-like molecules that inhibit Sec61, which may provide a new treatment for this cancer
Journal Reference :
Antoine Domenger, Caroline Choisy, Ludivine Baron, Véronique Mayau, Emeline Perthame, Ludovic Deriano, Bertrand Arnulf, Jean‐Christophe Bories, Gilles Dadaglio, Caroline Demangel.
The Sec61 translocon is a therapeutic vulnerability in multiple myeloma .
