Dataset Information

CDK9 inhibitors in acute myeloid leukemia.

ABSTRACT: Current treatment for acute myeloid leukemia (AML) is less than optimal, but increased understanding of disease pathobiology and genomics has led to clinical investigation of novel targeted therapies and rational combinations. Targeting the cyclin-dependent kinase 9 (CDK9) pathway, which is dysregulated in AML, is an attractive approach. Inhibition of CDK9 leads to downregulation of cell survival genes regulated by super enhancers such as MCL-1, MYC, and cyclin D1. As CDK9 inhibitors are nonselective, predictive biomarkers that may help identify patients most likely to respond to CDK9 inhibitors are now being utilized, with the goal of improving efficacy and safety.

SUBMITTER: Boffo S

PROVIDER: S-EPMC5824552 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

CDK9 inhibitors in acute myeloid leukemia.

Boffo Silvia S Damato Angela A Alfano Luigi L Giordano Antonio A

Journal of experimental & clinical cancer research : CR 20180223 1

Current treatment for acute myeloid leukemia (AML) is less than optimal, but increased understanding of disease pathobiology and genomics has led to clinical investigation of novel targeted therapies and rational combinations. Targeting the cyclin-dependent kinase 9 (CDK9) pathway, which is dysregulated in AML, is an attractive approach. Inhibition of CDK9 leads to downregulation of cell survival genes regulated by super enhancers such as MCL-1, MYC, and cyclin D1. As CDK9 inhibitors are nonsele ...[more]

PMID: 29471852

Similar Datasets

Project description:Mutations in the fms-like tyrosine kinase 3 (FLT3) gene are detected in approximately one-third of patients with newly diagnosed acute myeloid leukemia (AML). These consist of the more common FLT3-internal tandem duplication (ITD) in approximately 20-25% of AML cases, and point mutations in the tyrosine kinase domain (TKD) in approximately 5-10%. FLT3 mutations, especially FLT3-ITD, are associated with proliferative disease, increased risk of relapse, and inferior overall survival when treated with conventional regimens. However, the recent development of well tolerated and active FLT3 inhibitors has significantly improved the outcomes of this aggressive subtype of AML. The multikinase inhibitor midostaurin was approved by the United States Food and Drug Administration (US FDA) in April 2017 for the frontline treatment of patients with FLT3-mutated (either ITD or TKD) AML in combination with induction chemotherapy, representing the first new drug approval in AML in nearly two decades. In November 2018, the US FDA also approved the second-generation FLT3 inhibitor gilteritinib as a single agent for patients with relapsed or refractory FLT3-mutated AML. Promising phase I and II efficacy data for quizartinib is likely to lead to a third regulatory approval in relapsed/refractory AML in the near future. However, despite the significant progress made in managing FLT3-mutated AML, many questions remain regarding the best approach to integrate these inhibitors into combination regimens, and also the optimal sequencing of different FLT3 inhibitors in various clinical settings. This review comprehensively examines the FLT3 inhibitors currently in clinical development, with an emphasis on their spectra of activity against different FLT3 mutations and other kinases, clinical safety and efficacy data, and their current and future roles in the management of AML. The mechanisms of resistance to FLT3 inhibitors and potential combination strategies to overcome such resistance pathways are also discussed.

Dataset Information

CDK9 inhibitors in acute myeloid leukemia.

Publications

CDK9 inhibitors in acute myeloid leukemia.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure