Abstract
Simple SummaryMultiple myeloma (MM) is a plasma cell malignancy. Novel therapies have improved outcomes in MM patients; however, MM still remains incurable. MM cells present genomic instability, whose molecular basis is not fully understood. Recently, it has been reported that the DNA damage response (DDR) may influence genomic changes and drug resistance in MM. An abnormal DNA repair function may provide an alternative explanation for genomic instability. In this review, we show an overview of the DNA repair pathways and discuss the role of the tumor microenvironment in governing the DNA repair mechanisms. The tumor microenvironment factors, such as hypoxia and inflammation, and chemotherapeutic agents profoundly influence the DNA repair pathways in MM.Multiple myeloma (MM) is an incurable plasma cell malignancy characterized by genomic instability. MM cells present various forms of genetic instability, including chromosomal instability, microsatellite instability, and base-pair alterations, as well as changes in chromosome number. The tumor microenvironment and an abnormal DNA repair function affect genetic instability in this disease. In addition, states of the tumor microenvironment itself, such as inflammation and hypoxia, influence the DNA damage response, which includes DNA repair mechanisms, cell cycle checkpoints, and apoptotic pathways. Unrepaired DNA damage in tumor cells has been shown to exacerbate genomic instability and aberrant features that enable MM progression and drug resistance. This review provides an overview of the DNA repair pathways, with a special focus on their function in MM, and discusses the role of the tumor microenvironment in governing DNA repair mechanisms.
Highlights
Multiple myeloma (MM), which accounts for 1% of all cancers and approximately 10% of all hematologic malignancies, is characterized by the clonal proliferation of plasma cells [1,2]
The introduction of novel agents, bortezomib combined with lenalidomide plus dexamethasone, has improved the outcome of patients who are ineligible for autologous stem cell transplantation (ASCT) [7]
DNA Repair Pathways Mammalian cells have six major DNA repair pathways involved in the DDR: the base excision repair (BER), nucleotide excision repair (NER), and mismatch repair (MMR) pathways repair nucleotide lesions on single-stranded DNA (ssDNA); the homologous recombination (HR) and NHEJ pathways are involved in DSB repair; and the Fanconi anemia (FA) pathway repairs interstrand DNA crosslinks (ICLs) lesions in co-operation with the NER and HR pathways [23,24,25]
Summary
Multiple myeloma (MM), which accounts for 1% of all cancers and approximately 10% of all hematologic malignancies, is characterized by the clonal proliferation of plasma cells [1,2]. The introduction of novel agents, bortezomib combined with lenalidomide plus dexamethasone, has improved the outcome of patients who are ineligible for ASCT [7]. Carfilzomib [8], pomalidomide [9], panobinostat [10], ixazomib [11], of patients who are ineligible for ASCT [7]. DNA repair systems are important to protect DNA integrity, as the resolution of DNA damage lesions is critical for normal cells. DNA repair systems involve cell cycle checkpoints, removal of mutagenic lesions from DNA, and apoptosis or senescence if DNA repair fails [23,24], avoiding error information and interrupting neoplastic transformation [27]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
