The Emerging Therapeutic Landscape of ALK Inhibitors in Non-Small Cell Lung Cancer
The treatment of metastatic non-small cell lung cancer (NSCLC) has undergone a paradigm shift over the last decade. Better molecular characterization of the disease has led to the rapid improvement of personalized medicine and the prompt delivery of targeted therapies to patients with NSCLC. The dis...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-12-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/13/12/474 |
| _version_ | 1827699795891847168 |
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| author | Valerio Gristina Maria La Mantia Federica Iacono Antonio Galvano Antonio Russo Viviana Bazan |
| author_facet | Valerio Gristina Maria La Mantia Federica Iacono Antonio Galvano Antonio Russo Viviana Bazan |
| author_sort | Valerio Gristina |
| collection | DOAJ |
| description | The treatment of metastatic non-small cell lung cancer (NSCLC) has undergone a paradigm shift over the last decade. Better molecular characterization of the disease has led to the rapid improvement of personalized medicine and the prompt delivery of targeted therapies to patients with NSCLC. The discovery of the EML4-ALK fusion gene in a limited subset of patients affected by NSCLC and the subsequent clinical development of crizotinib in 2011 has been an impressive milestone in lung cancer research. Unfortunately, acquired resistances regularly develop, hence disease progression occurs. Afterward, modern tyrosine kinase inhibitors (TKIs), such as ceritinib, alectinib, brigatinib, and lorlatinib, have been approved by the Food and Drug Administration (FDA) for the management of anaplastic lymphoma kinase (ALK)-positive NSCLCs. Several compounds are currently under investigation to achieve the optimal strategy of therapy. Additionally, the results of ongoing clinical trials with novel-generation TKI will provide more evidence on the best sequence in the treatment of ALK-positive NSCLC patients. In this review, we provide a comprehensive overview of the state-of-the-art targeted therapy options in ALK-positive NSCLCs. Resistance, potential therapeutic strategies to overcome drug resistance, and future perspectives for this subset of patients are critically analyzed and summarized. |
| first_indexed | 2024-03-10T13:58:26Z |
| format | Article |
| id | doaj.art-b46216740dc641d9b409e5d8fb45ba0e |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-10T13:58:26Z |
| publishDate | 2020-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-b46216740dc641d9b409e5d8fb45ba0e2023-11-21T01:24:02ZengMDPI AGPharmaceuticals1424-82472020-12-01131247410.3390/ph13120474The Emerging Therapeutic Landscape of ALK Inhibitors in Non-Small Cell Lung CancerValerio Gristina0Maria La Mantia1Federica Iacono2Antonio Galvano3Antonio Russo4Viviana Bazan5Department of Surgical, Oncological and Oral Sciences, University of Palermo, 90127 Palermo, ItalyDepartment of Surgical, Oncological and Oral Sciences, University of Palermo, 90127 Palermo, ItalyDepartment of Surgical, Oncological and Oral Sciences, University of Palermo, 90127 Palermo, ItalyDepartment of Surgical, Oncological and Oral Sciences, University of Palermo, 90127 Palermo, ItalyDepartment of Surgical, Oncological and Oral Sciences, University of Palermo, 90127 Palermo, ItalyDepartment of Biomedicine, Neuroscience and Advanced Diagnostics (Bi.N.D.), Section of Medical Oncology, University of Palermo, 90127 Palermo, ItalyThe treatment of metastatic non-small cell lung cancer (NSCLC) has undergone a paradigm shift over the last decade. Better molecular characterization of the disease has led to the rapid improvement of personalized medicine and the prompt delivery of targeted therapies to patients with NSCLC. The discovery of the EML4-ALK fusion gene in a limited subset of patients affected by NSCLC and the subsequent clinical development of crizotinib in 2011 has been an impressive milestone in lung cancer research. Unfortunately, acquired resistances regularly develop, hence disease progression occurs. Afterward, modern tyrosine kinase inhibitors (TKIs), such as ceritinib, alectinib, brigatinib, and lorlatinib, have been approved by the Food and Drug Administration (FDA) for the management of anaplastic lymphoma kinase (ALK)-positive NSCLCs. Several compounds are currently under investigation to achieve the optimal strategy of therapy. Additionally, the results of ongoing clinical trials with novel-generation TKI will provide more evidence on the best sequence in the treatment of ALK-positive NSCLC patients. In this review, we provide a comprehensive overview of the state-of-the-art targeted therapy options in ALK-positive NSCLCs. Resistance, potential therapeutic strategies to overcome drug resistance, and future perspectives for this subset of patients are critically analyzed and summarized.https://www.mdpi.com/1424-8247/13/12/474non-small cell lung cancer (NSCLC)tyrosine kinase inhibitors (TKIs)ALK inhibitorscrizotinibceritinibalectinib |
| spellingShingle | Valerio Gristina Maria La Mantia Federica Iacono Antonio Galvano Antonio Russo Viviana Bazan The Emerging Therapeutic Landscape of ALK Inhibitors in Non-Small Cell Lung Cancer Pharmaceuticals non-small cell lung cancer (NSCLC) tyrosine kinase inhibitors (TKIs) ALK inhibitors crizotinib ceritinib alectinib |
| title | The Emerging Therapeutic Landscape of ALK Inhibitors in Non-Small Cell Lung Cancer |
| title_full | The Emerging Therapeutic Landscape of ALK Inhibitors in Non-Small Cell Lung Cancer |
| title_fullStr | The Emerging Therapeutic Landscape of ALK Inhibitors in Non-Small Cell Lung Cancer |
| title_full_unstemmed | The Emerging Therapeutic Landscape of ALK Inhibitors in Non-Small Cell Lung Cancer |
| title_short | The Emerging Therapeutic Landscape of ALK Inhibitors in Non-Small Cell Lung Cancer |
| title_sort | emerging therapeutic landscape of alk inhibitors in non small cell lung cancer |
| topic | non-small cell lung cancer (NSCLC) tyrosine kinase inhibitors (TKIs) ALK inhibitors crizotinib ceritinib alectinib |
| url | https://www.mdpi.com/1424-8247/13/12/474 |
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