Involvement of classic and alternative non-homologous end joining pathways in hematologic malignancies: targeting strategies for treatment

Experimental Hematology & Oncology

Seyed Esmaeil Ahmadi¹  Mohsen Valikhani¹  Majid Safa¹  Elahe Rahimian²  Rouzbeh Chegeni³ 

[1] Department of Hematology and Blood Banking, Faculty of Allied Medicine, School of Allied Medical Sciences, Iran University of Medical Sciences, Tehran, Iran;Department of Medical Translational Oncology, National Center for Tumor Diseases (NCT) Dresden, Dresden, Germany;Medical Laboratory Sciences, Program, College of Health and Human Sciences, Northern Illinois University, DeKalb, IL, USA;

关键词: Double-strand break;    Double-strand break repair;    Non-homologous end-joining;    Alternative end-joining pathways;    Hematologic malignancies;    Targeted therapy;   

DOI  :  10.1186/s40164-021-00242-1

来源: Springer

【 摘 要 】

Chromosomal translocations are the main etiological factor of hematologic malignancies. These translocations are generally the consequence of aberrant DNA double-strand break (DSB) repair. DSBs arise either exogenously or endogenously in cells and are repaired by major pathways, including non-homologous end-joining (NHEJ), homologous recombination (HR), and other minor pathways such as alternative end-joining (A-EJ). Therefore, defective NHEJ, HR, or A-EJ pathways force hematopoietic cells toward tumorigenesis. As some components of these repair pathways are overactivated in various tumor entities, targeting these pathways in cancer cells can sensitize them, especially resistant clones, to radiation or chemotherapy agents. However, targeted therapy-based studies are currently underway in this area, and furtherly there are some biological pitfalls, clinical issues, and limitations related to these targeted therapies, which need to be considered. This review aimed to investigate the alteration of DNA repair elements of C-NHEJ and A-EJ in hematologic malignancies and evaluate the potential targeted therapies against these pathways.

【 授权许可】

CC BY