Award 2020

Kim De Keersmaecker - KU Leuven Repurposing the antidepressant sertraline to target serine/glycine synthesis addicted cancer. Rewiring of energy metabolism is a key hallmark of cancer cells. In this regard, it recently became clear that certain cancers produce high levels of serine and glycine, and that these cancers get addicted to their own serine/glycine production to sustain their excessive growth. In the first part of this work, we showed that also acute lymphoblastic leukemia belongs to the rapidly expanding group of serine/glycine synthesis addicted cancers. The second part of this study aimed at identifying clinically applicable drugs that target serine/glycine synthesis, as this is a specific vulnerability in certain cancer cells but not in healthy cells. By screening serine/glycine synthesis addicted yeast and breast cancer cell models, we identified the clinically used anti-depressant sertraline (Serlain, Zoloft) as a specific inhibitor of serine/glycine synthesis. We showed that a drug combination including sertraline efficiently impairs proliferation of serine/glycine synthesis addicted breast cancer cells in a mouse model. Our work thus supports that sertraline has the potential to be an attractive adjuvant therapeutic agent to treat the rapidly growing list of serine/glycine synthesis addicted cancers. This research has been executed at the Laboratory for Disease Mechanisms in Cancer (www.LDMC.be) at the KU Leuven and the Leuven Cancer Institute (LKI). The research has also benefited of a close collaboration with the research group of Prof. Bruno Cammue (KU Leuven) via the IOF programme of Dr. Karin Thevissen and with the research groups of Prof. Sarah-Maria Fendt (KU Leuven – VIB) and Prof. Arnout Voet (KU Leuven). The use of sertraline as an anti-cancer drug has been patented (patent Pharmacological targeting of serine/glycine synthesis (PCT/EP2019/072826 27.08.2019)).