The Underlying Biology and Therapeutic Vulnerabilities of Leptomeningeal Metastases in Adult Solid Cancers
Metastasis to the central nervous system occurs in approximately 20% of patients with advanced solid cancers such as lung cancer, breast cancer, and melanoma. While central nervous system metastases most commonly form in the brain parenchyma, metastatic cancer cells may also reside in the subarachno...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-02-01
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| Series: | Cancers |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6694/13/4/732 |
| _version_ | 1797411689907355648 |
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| author | Matthew Dankner Stephanie Lam Theresa Degenhard Livia Garzia Marie-Christine Guiot Kevin Petrecca Peter M. Siegel |
| author_facet | Matthew Dankner Stephanie Lam Theresa Degenhard Livia Garzia Marie-Christine Guiot Kevin Petrecca Peter M. Siegel |
| author_sort | Matthew Dankner |
| collection | DOAJ |
| description | Metastasis to the central nervous system occurs in approximately 20% of patients with advanced solid cancers such as lung cancer, breast cancer, and melanoma. While central nervous system metastases most commonly form in the brain parenchyma, metastatic cancer cells may also reside in the subarachnoid space surrounding the brain and spinal cord to form tumors called leptomeningeal metastases. Leptomeningeal metastasis involves cancer cells that reach the subarachnoid space and proliferate in the cerebrospinal fluid compartment within the leptomeninges, a sequela associated with a myriad of symptoms and poor prognosis. Cancer cells exposed to cerebrospinal fluid in the leptomeninges must contend with a unique microenvironment from those that establish within the brain or other organs. Leptomeningeal lesions provide a formidable clinical challenge due to their often-diffuse infiltration within the subarachnoid space. The molecular mechanisms that promote the establishment of leptomeningeal metastases have begun to be elucidated, demonstrating that it is a biological entity distinct from parenchymal brain metastases and is associated with specific molecular drivers. In this review, we outline the current state of knowledge pertaining to the diagnosis, treatment, and molecular underpinnings of leptomeningeal metastasis. |
| first_indexed | 2024-03-09T04:49:42Z |
| format | Article |
| id | doaj.art-4aeefdb86554408ba0dcb394a7476e82 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T04:49:42Z |
| publishDate | 2021-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-4aeefdb86554408ba0dcb394a7476e822023-12-03T13:11:17ZengMDPI AGCancers2072-66942021-02-0113473210.3390/cancers13040732The Underlying Biology and Therapeutic Vulnerabilities of Leptomeningeal Metastases in Adult Solid CancersMatthew Dankner0Stephanie Lam1Theresa Degenhard2Livia Garzia3Marie-Christine Guiot4Kevin Petrecca5Peter M. Siegel6Goodman Cancer Research Centre, Faculty of Medicine, McGill University, Montreal, QC H3A 1A3, CanadaDepartment of Diagnostic Radiology, Faculty of Medicine, Research Institute of the McGill University Health Centre, Montreal, QC H3T 1E2, CanadaDepartment of Neurology and Neurosurgery, Montreal Neurological Institute-Hospital, Goodman Cancer Research Centre, McGill University, Montreal, QC H3A 2B4, CanadaResearch Institute of the McGill University Health Centre, Montreal, QC H4A 3J1, CanadaGoodman Cancer Research Centre, Faculty of Medicine, McGill University, Montreal, QC H3A 1A3, CanadaDepartment of Neurology and Neurosurgery, Montreal Neurological Institute-Hospital, Goodman Cancer Research Centre, McGill University, Montreal, QC H3A 2B4, CanadaGoodman Cancer Research Centre, Faculty of Medicine, McGill University, Montreal, QC H3A 1A3, CanadaMetastasis to the central nervous system occurs in approximately 20% of patients with advanced solid cancers such as lung cancer, breast cancer, and melanoma. While central nervous system metastases most commonly form in the brain parenchyma, metastatic cancer cells may also reside in the subarachnoid space surrounding the brain and spinal cord to form tumors called leptomeningeal metastases. Leptomeningeal metastasis involves cancer cells that reach the subarachnoid space and proliferate in the cerebrospinal fluid compartment within the leptomeninges, a sequela associated with a myriad of symptoms and poor prognosis. Cancer cells exposed to cerebrospinal fluid in the leptomeninges must contend with a unique microenvironment from those that establish within the brain or other organs. Leptomeningeal lesions provide a formidable clinical challenge due to their often-diffuse infiltration within the subarachnoid space. The molecular mechanisms that promote the establishment of leptomeningeal metastases have begun to be elucidated, demonstrating that it is a biological entity distinct from parenchymal brain metastases and is associated with specific molecular drivers. In this review, we outline the current state of knowledge pertaining to the diagnosis, treatment, and molecular underpinnings of leptomeningeal metastasis.https://www.mdpi.com/2072-6694/13/4/732brain metastasisleptomeningeal metastasessubarachnoid spacebreast cancerlung cancermelanoma |
| spellingShingle | Matthew Dankner Stephanie Lam Theresa Degenhard Livia Garzia Marie-Christine Guiot Kevin Petrecca Peter M. Siegel The Underlying Biology and Therapeutic Vulnerabilities of Leptomeningeal Metastases in Adult Solid Cancers Cancers brain metastasis leptomeningeal metastases subarachnoid space breast cancer lung cancer melanoma |
| title | The Underlying Biology and Therapeutic Vulnerabilities of Leptomeningeal Metastases in Adult Solid Cancers |
| title_full | The Underlying Biology and Therapeutic Vulnerabilities of Leptomeningeal Metastases in Adult Solid Cancers |
| title_fullStr | The Underlying Biology and Therapeutic Vulnerabilities of Leptomeningeal Metastases in Adult Solid Cancers |
| title_full_unstemmed | The Underlying Biology and Therapeutic Vulnerabilities of Leptomeningeal Metastases in Adult Solid Cancers |
| title_short | The Underlying Biology and Therapeutic Vulnerabilities of Leptomeningeal Metastases in Adult Solid Cancers |
| title_sort | underlying biology and therapeutic vulnerabilities of leptomeningeal metastases in adult solid cancers |
| topic | brain metastasis leptomeningeal metastases subarachnoid space breast cancer lung cancer melanoma |
| url | https://www.mdpi.com/2072-6694/13/4/732 |
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