FLT3 inhibitors and novel therapeutic strategies to reverse AML resistance: An updated comprehensive review

Abdel-Aziz, Amal Kamal; Dokla, Eman M E; Saadeldin, Mona Kamal;

Abstract


FMS-like tyrosine kinase 3 (FLT3) mutations occur in almost 30% of acute myeloid leukemia (AML) patients. Despite the initial clinical efficacy of FLT3 inhibitors, many treated AML patients with mutated FLT3 eventually relapse. This review critically discusses the opportunities and challenges of FLT3-targeted therapies and sheds light on their drug interactions as well as potential biomarkers. Furthermore, we focus on the molecular mechanisms underlying the resistance of FLT3 internal tandem duplication (FLT3-ITD) AMLs to FLT3 inhibitors alongside novel therapeutic strategies to reverse resistance. Notably, dynamic heterogeneous patterns of clonal selection and evolution contribute to the resistance of FLT3-ITD AMLs to FLT3 inhibitors. Ongoing preclinical research and clinical trials are actively directed towards devising rational "personalized" or "patient-tailored" combinatorial therapeutic regimens to effectively treat patients with FLT3 mutated AML.


Other data

Title FLT3 inhibitors and novel therapeutic strategies to reverse AML resistance: An updated comprehensive review
Authors Abdel-Aziz, Amal Kamal ; Dokla, Eman M E; Saadeldin, Mona Kamal
Keywords AML; Biomarker; Drug interaction; FLT3 mutation; Resistance; Toxicity
Issue Date Nov-2023
Journal Critical reviews in oncology/hematology 
ISSN 10408428
DOI 10.1016/j.critrevonc.2023.104139
PubMed ID 37717880
Scopus ID 2-s2.0-85172274952

Recommend this item

Similar Items from Core Recommender Database

Google ScholarTM

Check



Items in Ain Shams Scholar are protected by copyright, with all rights reserved, unless otherwise indicated.