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Project

Serine/glycine synthesis addiction in acute lymphoblastic leukemia and resulting therapeutic opportunities

Acute lymphoblastic leukemia (ALL) is the most common childhood cancer.
While overall survival reaches >90%, lethality due to therapy failure or
relapse, and long-term toxicity remain serious problems. While most healthy
cells take up serine/glycine from their environment, some cancer cells
activate endogenous serine/glycine production and become addicted to this
pathway to support their proliferation. We previously identified two genetics
lesions that induce serine/glycine synthesis dependence in ALL, allowing to
delineate patients that will benefit from targeting serine/glycine synthesis.
We aim to investigate whether loss of transcription factor IKZF1 in ALL also
defines a serine/glycine synthesis addicted subgroup. Furthermore, we
identified a repurposed clinical drug (sertraline) that targets the
serine/glycine synthesis pathway. Sertraline will be investigated in
combination therapy to improve the therapeutic responses in serine/glycine
synthesis addicted ALL cell line and PDX mouse models, with the ultimate
goal to target ALL cells more specifically and reduce the therapy-associated
toxicity.

Date:1 Mar 2021 →  Today
Keywords:drug discovery, small molecules, metabolomics, acute lymphoblastic leukemia
Disciplines:Hematology, Drug discovery and development not elsewhere classified, Medical metabolomics