Resistance to Targeted Therapies: Delving Into FLT3 and IDH

Authors

Sai Prasad Desikan
Naval Daver
Courtney DiNardo
Tapan Kadia
Marina Konopleva
Farhad Ravandi

Publication Date

6-9-2022

Journal

Blood Cancer Journal

Abstract

Recent advances in FLT3 and IDH targeted inhibition have improved response rates and overall survival in patients with mutations affecting these respective proteins. Despite this success, resistance mechanisms have arisen including mutations that disrupt inhibitor-target interaction, mutations impacting alternate pathways, and changes in the microenvironment. Here we review the role of these proteins in leukemogenesis, their respective inhibitors, mechanisms of resistance, and briefly ongoing studies aimed at overcoming resistance.

Keywords

Drug Resistance, Neoplasm, Humans, Leukemia, Myeloid, Acute, Mutation, Protein Kinase Inhibitors, Tumor Microenvironment, fms-Like Tyrosine Kinase 3

DOI

10.1038/s41408-022-00687-5

PMID

35680852

PMCID

PMC9184476

PubMedCentral® Posted Date

6-9-2022

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes