Discovery points to blood cancer therapy with fewer side-effects
5 Jul 2017
MRC-funded scientists have gained new insight into a signalling process inside cells that could lead to blood cancer chemotherapy with fewer side effects.
The researchers used stem cells to study small chemical packages that are released by cells in order to send signals to the surrounding environment. They discovered that these packages – extracellular vesicles – have the specific enzyme activity required to kill cancer cells, without starving healthy cells of the essential nutrients they need to function.
The most active enzyme in the vesicles was found to be Asparaginase-like-1. This is a variant of an enzyme called L-Asparaginase which is used as a chemotherapy for acute lymphoblastic leukaemia, a blood cancer often diagnosed in younger people.
L-Asparaginase chemotherapy works by reducing levels of asparagine, a naturally occurring chemical in the body that cancer cells need to survive. However, an unwanted side-effect of the drug is that it also depletes a chemical called glutamine, which the healthy cells in the body need in order to function normally.
The scientists discovered that Asparaginase-like-1, the enzyme they were studying in the vesicles, acted specifically to break down asparagine, without affecting levels of glutamine. This unexpected property suggests a way to develop new chemotherapy with fewer side effects.
The University of Cambridge research team was led by Dr Stefano Pluchino from the Wellcome Trust – MRC Cambridge Stem Cell Institute, and Dr Christian Frezza from the MRC Cancer Unit.
Dr Pluchino explains: “Current drug treatment 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.
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 limit side effects such as liver toxicity that can occur when glutamine is depleted”.
Dr Nathan Richardson, the MRC’s Head of Molecular and Cellular Medicine, added: “This exciting discovery sheds light on how stem cells communicate with their surrounding tissue, and has the potential to lead to better tolerated cancer treatments. This illustrates the merit of supporting discovery research addressing cellular and disease mechanisms and the unanticipated benefits that can sometimes be realised”.
The original research paper, ‘Extracellular vesicles are independent metabolic units with asparaginase activity’ was published 3 July 2017 in Nature Chemical Biology and the research was co-funded by the MRC, the European Research Council, the Italian Multiple Sclerosis Association, the UK Regenerative Medicine Platform’, the Evelyn Trust and the Bascule Charitable Trust.