Biological Pathway: Reactome:R-HSA-9702506

Drug resistance of FLT3 mutants related metabolites

find 6 related metabolites which is associated with the biological pathway Drug resistance of FLT3 mutants

this pathway object is a organism specific pathway, which is related to taxonomy Homo sapiens (human).

FLT3 is mutated in ~30\% of acute myeloid leukemias (AML), with internal tandem duplications (ITDs) representing the majority of these mutations and activating point mutants occurring at lower frequency. FLT3 mutations also occur at lower rates in other cancers (reviewed in Kazi and Roonstrand, 2018; Daver et al, 2019; Larroas-Garcia and Baer, 2017). Mutation of FLT3 has been identified as a driver in progression of AML and in consequence is a promising therapeutic target. A number of first and second generation inhibitors have been demonstrated to have activity against FLT3, but accumulation of secondary mutations leads to the development of resistance. These secondary mutations further shift the equilibrium of the receptor toward the activated state, making even the second-generation type II TKIs less effective. In consequence, considerable effort is devoted to discovery of type II and, in particular, type I TKIs that are active against highly activated FLT3 alleles (reviewed in Daver et al, 2019; Staudt et al, 2018; Lim et al, 2017; Klug et al, 2018).