Investigational CHK1 inhibitors in early stage clinical trials for acute myeloid leukemia
K Chamoun, G Borthakur - Expert opinion on investigational drugs, 2018 - Taylor & Francis
K Chamoun, G Borthakur
Expert opinion on investigational drugs, 2018•Taylor & FrancisIntroduction: 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 …
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 …
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.
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