Awakening of Dormant Breast Cancer Cells in the Bone Marrow
Up to 40% of patients with breast cancer (BC) have metastatic cells in the bone marrow (BM) at the initial diagnosis of localized disease. Despite definitive systemic adjuvant therapy, these cells survive in the BM microenvironment, enter a dormant state and recur stochastically for more than 20 yea...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-06-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/15/11/3021 |
| _version_ | 1797597788672884736 |
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| author | Robert Wieder |
| author_facet | Robert Wieder |
| author_sort | Robert Wieder |
| collection | DOAJ |
| description | Up to 40% of patients with breast cancer (BC) have metastatic cells in the bone marrow (BM) at the initial diagnosis of localized disease. Despite definitive systemic adjuvant therapy, these cells survive in the BM microenvironment, enter a dormant state and recur stochastically for more than 20 years. Once they begin to proliferate, recurrent macrometastases are not curable, and patients generally succumb to their disease. Many potential mechanisms for initiating recurrence have been proposed, but no definitive predictive data have been generated. This manuscript reviews the proposed mechanisms that maintain BC cell dormancy in the BM microenvironment and discusses the data supporting specific mechanisms for recurrence. It addresses the well-described mechanisms of secretory senescence, inflammation, aging, adipogenic BM conversion, autophagy, systemic effects of trauma and surgery, sympathetic signaling, transient angiogenic bursts, hypercoagulable states, osteoclast activation, and epigenetic modifications of dormant cells. This review addresses proposed approaches for either eliminating micrometastases or maintaining a dormant state. |
| first_indexed | 2024-03-11T03:10:24Z |
| format | Article |
| id | doaj.art-406eeb94fc6d4cedab79ad1b5ca233aa |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-11T03:10:24Z |
| publishDate | 2023-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-406eeb94fc6d4cedab79ad1b5ca233aa2023-11-18T07:39:40ZengMDPI AGCancers2072-66942023-06-011511302110.3390/cancers15113021Awakening of Dormant Breast Cancer Cells in the Bone MarrowRobert Wieder0Rutgers New Jersey Medical School and the Cancer Institute of New Jersey, 185 South Orange Avenue, MSB F671, Newark, NJ 07103, USAUp to 40% of patients with breast cancer (BC) have metastatic cells in the bone marrow (BM) at the initial diagnosis of localized disease. Despite definitive systemic adjuvant therapy, these cells survive in the BM microenvironment, enter a dormant state and recur stochastically for more than 20 years. Once they begin to proliferate, recurrent macrometastases are not curable, and patients generally succumb to their disease. Many potential mechanisms for initiating recurrence have been proposed, but no definitive predictive data have been generated. This manuscript reviews the proposed mechanisms that maintain BC cell dormancy in the BM microenvironment and discusses the data supporting specific mechanisms for recurrence. It addresses the well-described mechanisms of secretory senescence, inflammation, aging, adipogenic BM conversion, autophagy, systemic effects of trauma and surgery, sympathetic signaling, transient angiogenic bursts, hypercoagulable states, osteoclast activation, and epigenetic modifications of dormant cells. This review addresses proposed approaches for either eliminating micrometastases or maintaining a dormant state.https://www.mdpi.com/2072-6694/15/11/3021dormancymicrometastaseshematopoietic nichebone marrow microenvironmentosteoblast nichereawakening |
| spellingShingle | Robert Wieder Awakening of Dormant Breast Cancer Cells in the Bone Marrow Cancers dormancy micrometastases hematopoietic niche bone marrow microenvironment osteoblast niche reawakening |
| title | Awakening of Dormant Breast Cancer Cells in the Bone Marrow |
| title_full | Awakening of Dormant Breast Cancer Cells in the Bone Marrow |
| title_fullStr | Awakening of Dormant Breast Cancer Cells in the Bone Marrow |
| title_full_unstemmed | Awakening of Dormant Breast Cancer Cells in the Bone Marrow |
| title_short | Awakening of Dormant Breast Cancer Cells in the Bone Marrow |
| title_sort | awakening of dormant breast cancer cells in the bone marrow |
| topic | dormancy micrometastases hematopoietic niche bone marrow microenvironment osteoblast niche reawakening |
| url | https://www.mdpi.com/2072-6694/15/11/3021 |
| work_keys_str_mv | AT robertwieder awakeningofdormantbreastcancercellsinthebonemarrow |