Investigational CHK1 inhibitors in early stage clinical trials for acute myeloid leukemia. (3rd August 2018)

• Record Type: Journal Article
• Authors: Chamoun, Kamal; Borthakur, Gautam
• Is Part Of: Expert opinion on investigational drugs. Volume 27:Number 8(2018)
• Page Start: 661
• Page End: 666
• Publication Date: 2018-08-03
• Subjects: CHK1 inhibitor -- DNA damage repair pathway -- cell cycle inhibitors -- acute myeloid leukemia; Drugs -- Design -- Periodicals; Drugs, Investigational -- Bibliography; Drugs, Investigational -- Periodicals; 615.1
• DOI: 10.1080/13543784.2018.1508448
• Languages: English
• ISSNs: 1354-3784

Abstract

ABSTRACT: Introduction : Acute myeloid leukemia (AML) is the most common myeloid malignancy in adults. Despite recent discoveries of targeted therapies, the frontline therapy consisting of chemotherapy remains unchanged for the past four decades. Like other cancers, AML is characterized by deranged DNA damage repair (DDR) pathway. Although impaired DDR may contribute to the pathogenesis of AML it also allows leukemia cells with damaged DNA to attempt repair resulting in resistance. CHK1 inhibitors reverse the cell cycle arrest, disallowing the cell to repair the chemotherapy-induced DNA damage, driving the cell to enter into mitotic catastrophe. Areas covered : This paper reviews the preclinical and clinical development of CHK1 inhibitors and we discussed their promising role as a potential addition to the therapeutic arsenal of AML. Expert opinion : Targeting the cell cycle checkpoints is an intriguing approach to treat cancer in general and AML in particular. CHK1 inhibitors in combination with chemotherapy have the potential of improving outcome in high-risk AML characterized by DDR activation.