Partnering with PARP inhibitors in acute myeloid leukemia with FLT3-ITD.

ABSTRACT: Internal tandem duplications within the juxtamembrane domain of fms-like tyrosine kinase 3 (FLT3-ITD) occur in acute myeloid leukemia (AML) cells of 20-25% of patients and are associated with poor treatment outcomes. FLT3 inhibitors have been developed, but have had limited clinical efficacy due to development of resistance, highlighting the need for better understanding of the function of FLT3-ITD and how to target it more effectively using novel combination strategies. Poly (ADP-ribose) polymerase (PARP) inhibitors have shown efficacy in cancers with impaired homologous recombination (HR) due to BRCA mutations, but PARP inhibitor efficacy has not been fully explored in BRCA-proficient cancers, including AML. Recent research has connected inhibition of FLT3-ITD signaling to downregulation

SUBMITTER: Dellomo AJ 

PROVIDER: S-EPMC6528833 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature