Understanding DNA Damage Response and DNA Repair in Multiple Myeloma
Multiple myeloma (MM) is a plasma cell malignancy characterized by several genetic abnormalities, including chromosomal translocations, genomic deletions and gains, and point mutations. DNA damage response (DDR) and DNA repair mechanisms are altered in MM to allow for tumor development, progression,...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-08-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/15/16/4155 |
| _version_ | 1797585234931220480 |
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| author | Cole Petrilla Joshua Galloway Ruchi Kudalkar Aya Ismael Francesca Cottini |
| author_facet | Cole Petrilla Joshua Galloway Ruchi Kudalkar Aya Ismael Francesca Cottini |
| author_sort | Cole Petrilla |
| collection | DOAJ |
| description | Multiple myeloma (MM) is a plasma cell malignancy characterized by several genetic abnormalities, including chromosomal translocations, genomic deletions and gains, and point mutations. DNA damage response (DDR) and DNA repair mechanisms are altered in MM to allow for tumor development, progression, and resistance to therapies. Damaged DNA rarely induces an apoptotic response, given the presence of ataxia-telangiectasia mutated (<i>ATM</i>) loss-of-function or mutations, as well as deletions, mutations, or downregulation of tumor protein p53 (TP53) and tumor protein p73 (TP73). Moreover, DNA repair mechanisms are either hyperactive or defective to allow for rapid correction of the damage or permissive survival. Medications used to treat patients with MM can induce DNA damage, by either direct effects (mono-adducts induced by melphalan), or as a result of reactive oxygen species (ROS) production by proteasome inhibitors such as bortezomib. In this review, we will describe the mechanisms of DDR and DNA repair in normal tissues, the contribution of these pathways to MM disease progression and other phenotypes, and the potential therapeutic opportunities for patients with MM. |
| first_indexed | 2024-03-11T00:03:11Z |
| format | Article |
| id | doaj.art-42dcec98edf34c42b714f85624be67bd |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-11T00:03:11Z |
| publishDate | 2023-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-42dcec98edf34c42b714f85624be67bd2023-11-19T00:34:05ZengMDPI AGCancers2072-66942023-08-011516415510.3390/cancers15164155Understanding DNA Damage Response and DNA Repair in Multiple MyelomaCole Petrilla0Joshua Galloway1Ruchi Kudalkar2Aya Ismael3Francesca Cottini4Division of Hematology, Department of Internal Medicine, College of Medicine, The Ohio State University, Columbus, OH 43210, USADivision of Hematology, Department of Internal Medicine, College of Medicine, The Ohio State University, Columbus, OH 43210, USADivision of Hematology, Department of Internal Medicine, College of Medicine, The Ohio State University, Columbus, OH 43210, USADivision of Hematology, Department of Internal Medicine, College of Medicine, The Ohio State University, Columbus, OH 43210, USADivision of Hematology, Department of Internal Medicine, College of Medicine, The Ohio State University, Columbus, OH 43210, USAMultiple myeloma (MM) is a plasma cell malignancy characterized by several genetic abnormalities, including chromosomal translocations, genomic deletions and gains, and point mutations. DNA damage response (DDR) and DNA repair mechanisms are altered in MM to allow for tumor development, progression, and resistance to therapies. Damaged DNA rarely induces an apoptotic response, given the presence of ataxia-telangiectasia mutated (<i>ATM</i>) loss-of-function or mutations, as well as deletions, mutations, or downregulation of tumor protein p53 (TP53) and tumor protein p73 (TP73). Moreover, DNA repair mechanisms are either hyperactive or defective to allow for rapid correction of the damage or permissive survival. Medications used to treat patients with MM can induce DNA damage, by either direct effects (mono-adducts induced by melphalan), or as a result of reactive oxygen species (ROS) production by proteasome inhibitors such as bortezomib. In this review, we will describe the mechanisms of DDR and DNA repair in normal tissues, the contribution of these pathways to MM disease progression and other phenotypes, and the potential therapeutic opportunities for patients with MM.https://www.mdpi.com/2072-6694/15/16/4155multiple myelomaDNA damage responseDNA repair |
| spellingShingle | Cole Petrilla Joshua Galloway Ruchi Kudalkar Aya Ismael Francesca Cottini Understanding DNA Damage Response and DNA Repair in Multiple Myeloma Cancers multiple myeloma DNA damage response DNA repair |
| title | Understanding DNA Damage Response and DNA Repair in Multiple Myeloma |
| title_full | Understanding DNA Damage Response and DNA Repair in Multiple Myeloma |
| title_fullStr | Understanding DNA Damage Response and DNA Repair in Multiple Myeloma |
| title_full_unstemmed | Understanding DNA Damage Response and DNA Repair in Multiple Myeloma |
| title_short | Understanding DNA Damage Response and DNA Repair in Multiple Myeloma |
| title_sort | understanding dna damage response and dna repair in multiple myeloma |
| topic | multiple myeloma DNA damage response DNA repair |
| url | https://www.mdpi.com/2072-6694/15/16/4155 |
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