Effectiveness of ALK inhibitors in treatment of CNS metastases in NSCLC patients
AbstractMetastases to the central nervous system (CNS) in patients with non-small cell lung cancer constitute an extremely difficult clinical problem, and their occurrence is associated with a poor prognosis. Due to the existence of the blood-brain barrier (BBB) and the action of proteins responsibl...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2023-12-01
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| Series: | Annals of Medicine |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/07853890.2023.2187077 |
| _version_ | 1797353769913024512 |
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| author | Michał Gil Magdalena Knetki-Wróblewska Przemysław Niziński Maciej Strzemski Paweł Krawczyk |
| author_facet | Michał Gil Magdalena Knetki-Wróblewska Przemysław Niziński Maciej Strzemski Paweł Krawczyk |
| author_sort | Michał Gil |
| collection | DOAJ |
| description | AbstractMetastases to the central nervous system (CNS) in patients with non-small cell lung cancer constitute an extremely difficult clinical problem, and their occurrence is associated with a poor prognosis. Due to the existence of the blood-brain barrier (BBB) and the action of proteins responsible for the transport of drugs, e.g. P-glycoprotein (P-gp), the penetration of drugs into the CNS is insufficient. Until recently, the only method of CNS metastases treatment was radiotherapy and neurosurgery. The advancement of molecular biology allowed discover targets for molecularly targeted therapies. One of targets is abnormal anaplastic lymphoma kinase, which results from the rearrangement of the ALK gene in patients with non-small cell lung cancer (NSCLC). ALK rearrangement occurs in only about 4.5% of NSCLC patients, but its presence favors brain metastases. The ALK inhibitors (ALKi) were modified to obtain molecules with high ability to penetrate into the CNS. This was achieved by modifying the structure of individual molecules, which became, inter alia, less substrates for P-gp. These modifications caused that less than 10% of patients experience progression in CNS during new ALK inhibitors treatment. This review summarizes the knowledge about the action of BBB, the pharmacodynamics and pharmacokinetics of ALKi, with particular emphasis on their ability to penetrate the CNS and the intracranial activity of individual drugs from different generations of ALK inhibitors. |
| first_indexed | 2024-03-08T13:35:49Z |
| format | Article |
| id | doaj.art-d944926d500c4a3c80977ba12df8b70e |
| institution | Directory Open Access Journal |
| issn | 0785-3890 1365-2060 |
| language | English |
| last_indexed | 2024-03-08T13:35:49Z |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Annals of Medicine |
| spelling | doaj.art-d944926d500c4a3c80977ba12df8b70e2024-01-16T19:13:21ZengTaylor & Francis GroupAnnals of Medicine0785-38901365-20602023-12-015511018102810.1080/07853890.2023.2187077Effectiveness of ALK inhibitors in treatment of CNS metastases in NSCLC patientsMichał Gil0Magdalena Knetki-Wróblewska1Przemysław Niziński2Maciej Strzemski3Paweł Krawczyk4Department of Pneumonology, Oncology and Allergology, Medical University of Lublin, Lublin, PolandDepartment of Lung Cancer and Chest Tumors, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, PolandDepartment of Pharmacology, Medical University of Lublin, Lublin, PolandDepartment of Analytical Chemistry, Medical University of Lublin, Lublin, PolandDepartment of Pneumonology, Oncology and Allergology, Medical University of Lublin, Lublin, PolandAbstractMetastases to the central nervous system (CNS) in patients with non-small cell lung cancer constitute an extremely difficult clinical problem, and their occurrence is associated with a poor prognosis. Due to the existence of the blood-brain barrier (BBB) and the action of proteins responsible for the transport of drugs, e.g. P-glycoprotein (P-gp), the penetration of drugs into the CNS is insufficient. Until recently, the only method of CNS metastases treatment was radiotherapy and neurosurgery. The advancement of molecular biology allowed discover targets for molecularly targeted therapies. One of targets is abnormal anaplastic lymphoma kinase, which results from the rearrangement of the ALK gene in patients with non-small cell lung cancer (NSCLC). ALK rearrangement occurs in only about 4.5% of NSCLC patients, but its presence favors brain metastases. The ALK inhibitors (ALKi) were modified to obtain molecules with high ability to penetrate into the CNS. This was achieved by modifying the structure of individual molecules, which became, inter alia, less substrates for P-gp. These modifications caused that less than 10% of patients experience progression in CNS during new ALK inhibitors treatment. This review summarizes the knowledge about the action of BBB, the pharmacodynamics and pharmacokinetics of ALKi, with particular emphasis on their ability to penetrate the CNS and the intracranial activity of individual drugs from different generations of ALK inhibitors.https://www.tandfonline.com/doi/10.1080/07853890.2023.2187077Non-small cell lung canceranaplastic lymphoma kinaseblood-brain barrierALK inhibitors |
| spellingShingle | Michał Gil Magdalena Knetki-Wróblewska Przemysław Niziński Maciej Strzemski Paweł Krawczyk Effectiveness of ALK inhibitors in treatment of CNS metastases in NSCLC patients Annals of Medicine Non-small cell lung cancer anaplastic lymphoma kinase blood-brain barrier ALK inhibitors |
| title | Effectiveness of ALK inhibitors in treatment of CNS metastases in NSCLC patients |
| title_full | Effectiveness of ALK inhibitors in treatment of CNS metastases in NSCLC patients |
| title_fullStr | Effectiveness of ALK inhibitors in treatment of CNS metastases in NSCLC patients |
| title_full_unstemmed | Effectiveness of ALK inhibitors in treatment of CNS metastases in NSCLC patients |
| title_short | Effectiveness of ALK inhibitors in treatment of CNS metastases in NSCLC patients |
| title_sort | effectiveness of alk inhibitors in treatment of cns metastases in nsclc patients |
| topic | Non-small cell lung cancer anaplastic lymphoma kinase blood-brain barrier ALK inhibitors |
| url | https://www.tandfonline.com/doi/10.1080/07853890.2023.2187077 |
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