Targeting WEE1 kinase as a p53-independent therapeutic strategy in high-risk and relapsed acute lymphoblastic leukemia.

ABSTRACT:

Background

Outcomes for patients with relapsed acute lymphoblastic leukemia (ALL) are poor and there is a need for novel therapies to improve outcomes. Targeted inhibition of WEE1 with small-molecule inhibitor adavosertib (AZD1775) has emerged as a therapeutic strategy to sensitize cancer cells to DNA-damaging chemotherapeutics, particularly in the context of TP53-mutated tumors. However, WEE1 inhibition as a potential therapeutic strategy for patients with high-risk and relapsed ALL, including those with TP53 mutations, has not been definitively evaluated.

Methods

Anti-leukemic effects of adavosertib were investigated using a relapsed TP53 isogenic cell model system, primary patient, and patient-derived ALL samples (n = 27) in an ex vivo co-culture model system with bone ma

SUBMITTER: Bell HL 

PROVIDER: S-EPMC10502974 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature