Targeting the DNA damage response in hematological malignancies.

Autor:	De Mel S; Department of Haematology-Oncology, National University Cancer Institute, Singapore, National University Health System, Singapore, Singapore.; Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.; NUS Center for Cancer Research (N2CR), Yong Loo Lin School of Medicine, National University Singapore, Singapore, Singapore., Lee AR; Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore., Tan JHI; Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore., Tan RZY; Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore., Poon LM; Department of Haematology-Oncology, National University Cancer Institute, Singapore, National University Health System, Singapore, Singapore.; NUS Center for Cancer Research (N2CR), Yong Loo Lin School of Medicine, National University Singapore, Singapore, Singapore., Chan E; Department of Haematology-Oncology, National University Cancer Institute, Singapore, National University Health System, Singapore, Singapore.; NUS Center for Cancer Research (N2CR), Yong Loo Lin School of Medicine, National University Singapore, Singapore, Singapore., Lee J; Department of Haematology-Oncology, National University Cancer Institute, Singapore, National University Health System, Singapore, Singapore.; NUS Center for Cancer Research (N2CR), Yong Loo Lin School of Medicine, National University Singapore, Singapore, Singapore., Chee YL; Department of Haematology-Oncology, National University Cancer Institute, Singapore, National University Health System, Singapore, Singapore.; NUS Center for Cancer Research (N2CR), Yong Loo Lin School of Medicine, National University Singapore, Singapore, Singapore., Lakshminarasappa SR; Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore., Jaynes PW; Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore., Jeyasekharan AD; Department of Haematology-Oncology, National University Cancer Institute, Singapore, National University Health System, Singapore, Singapore.; Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.; NUS Center for Cancer Research (N2CR), Yong Loo Lin School of Medicine, National University Singapore, Singapore, Singapore.; Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.
Jazyk:	angličtina
Zdroj:	Frontiers in oncology [Front Oncol] 2024 Jan 29; Vol. 14, pp. 1307839. Date of Electronic Publication: 2024 Jan 29 (Print Publication: 2024).
DOI:	10.3389/fonc.2024.1307839
Abstrakt:	Deregulation of the DNA damage response (DDR) plays a critical role in the pathogenesis and progression of many cancers. The dependency of certain cancers on DDR pathways has enabled exploitation of such through synthetically lethal relationships e.g., Poly ADP-Ribose Polymerase (PARP) inhibitors for BRCA deficient ovarian cancers. Though lagging behind that of solid cancers, DDR inhibitors (DDRi) are being clinically developed for haematological cancers. Furthermore, a high proliferative index characterize many such cancers, suggesting a rationale for combinatorial strategies targeting DDR and replicative stress. In this review, we summarize pre-clinical and clinical data on DDR inhibition in haematological malignancies and highlight distinct haematological cancer subtypes with activity of DDR agents as single agents or in combination with chemotherapeutics and targeted agents. We aim to provide a framework to guide the design of future clinical trials involving haematological cancers for this important class of drugs. Competing Interests: AJ has received consultancy fees from Roche, Gilead, Turbine Ltd, AstraZeneca, Antegene, Janssen, MSD and IQVIA; and research funding from Janssen and AstraZeneca. SD has been on advisory boards for Amgen and Pfizer. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2024 De Mel, Lee, Tan, Tan, Poon, Chan, Lee, Chee, Lakshminarasappa, Jaynes and Jeyasekharan.)
Databáze:	MEDLINE
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