In a recent study published in Nature Chemical Biology, researchers from the WT-MRC Cambridge Stem Cell Institute, the MRC Cancer Unit and the Department of Clinical Neurosciences have revealed new insights into cellular signalling processes that could improve chemotherapy treatments.
The research team, led by Dr Stefano Pluchino and Dr Christian Frezza, used stem cells to identify that small signalling packages (known as extracellular vesicles) have the specific enzyme activity required to kill some cancer cells, without depleting essential nutrients required for healthy cell function. Using a series of functional analyses as well as targeted and untargeted metabolomics analyses, co-first authors, Nunzio Iraci and Edoardo Gaude, isolated these vesicles and measured their enzyme activity. The most active enzyme was found to be Asparaginase-like 1, a variant of the enzyme used in the treatment of acute lymphoblastic leukaemia, a blood cancer often diagnosed in younger people.
In the treatment of cancers, the chemotherapy enzyme works by depleting asparagine, a naturally occurring chemical in the body that cancer cells need to survive. However, the treatment also depletes a chemical called glutamine, which the healthy cells in the body need in order to function normally. The researchers found that the activity of Asparaginase-like 1 enzyme in the isolated vesicles acted specifically on breaking down asparagine, and importantly, did not affect the levels of glutamine.
“Current drug treatments of acute lymphoblastic leukaemia presents a difficult balancing act: removing enough asparagine so that cancer cells cannot survive, but leaving enough glutamine to ensure normal cells in the body can thrive”, explains Dr Pluchino. “The discovery that the Asparaginase-like 1 in vesicles depletes asparagine but does not affect the glutamine could provide an alternative anti-cancer therapy that could limits the side effects such as liver toxicity that can occur when glutamine is depleted”. Read more