Focus on ROS1-Positive Non-Small Cell Lung Cancer (NSCLC): Crizotinib, Resistance Mechanisms and the Newer Generation of Targeted Therapies
The treatment of patients affected by non-small cell lung cancer (NSCLC) has been revolutionised by the discovery of druggable mutations. ROS1 (c-ros oncogene) is one gene with druggable mutations in NSCLC. ROS1 is currently targeted by several specific tyrosine kinase inhibitors (TKIs), but only tw...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-11-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/12/11/3293 |
| _version_ | 1797548610768863232 |
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| author | Alberto D’Angelo Navid Sobhani Robert Chapman Stefan Bagby Carlotta Bortoletti Mirko Traversini Katia Ferrari Luca Voltolini Jacob Darlow Giandomenico Roviello |
| author_facet | Alberto D’Angelo Navid Sobhani Robert Chapman Stefan Bagby Carlotta Bortoletti Mirko Traversini Katia Ferrari Luca Voltolini Jacob Darlow Giandomenico Roviello |
| author_sort | Alberto D’Angelo |
| collection | DOAJ |
| description | The treatment of patients affected by non-small cell lung cancer (NSCLC) has been revolutionised by the discovery of druggable mutations. ROS1 (c-ros oncogene) is one gene with druggable mutations in NSCLC. ROS1 is currently targeted by several specific tyrosine kinase inhibitors (TKIs), but only two of these, crizotinib and entrectinib, have received Food and Drug Administration (FDA) approval. Crizotinib is a low molecular weight, orally available TKI that inhibits ROS1, MET and ALK and is considered the gold standard first-line treatment with demonstrated significant activity for lung cancers harbouring ROS1 gene rearrangements. However, crizotinib resistance often occurs, making the treatment of ROS1-positive lung cancers more challenging. A great effort has been undertaken to identify a new generation or ROS1 inhibitors. In this review, we briefly introduce the biology and role of ROS1 in lung cancer and discuss the underlying acquired mechanisms of resistance to crizotinib and the promising new agents able to overcome resistance mechanisms and offer alternative efficient therapies. |
| first_indexed | 2024-03-10T15:03:02Z |
| format | Article |
| id | doaj.art-6223cdd35a92474e837a7f49247e028b |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T15:03:02Z |
| publishDate | 2020-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-6223cdd35a92474e837a7f49247e028b2023-11-20T20:02:29ZengMDPI AGCancers2072-66942020-11-011211329310.3390/cancers12113293Focus on ROS1-Positive Non-Small Cell Lung Cancer (NSCLC): Crizotinib, Resistance Mechanisms and the Newer Generation of Targeted TherapiesAlberto D’Angelo0Navid Sobhani1Robert Chapman2Stefan Bagby3Carlotta Bortoletti4Mirko Traversini5Katia Ferrari6Luca Voltolini7Jacob Darlow8Giandomenico Roviello9Department of Biology and Biochemistry, University of Bath, Bath BA2 7AY, UKSection of Epidemiology and Population Science, Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USAUniversity College London Hospitals NHS Foundation Trust, 235 Euston Rd, London NW1 2BU, UKDepartment of Biology and Biochemistry, University of Bath, Bath BA2 7AY, UKDepartment of Dermatology, University of Padova, via Vincenzo Gallucci 4, 35121 Padova, ItalyUnità Operativa Anatomia Patologica, Ospedale Maggiore Carlo Alberto Pizzardi, AUSL Bologna, Largo Bartolo Nigrisoli 2, 40100 Bologna, ItalyRespiratory Medicine, Careggi University Hospital, 50139 Florence, ItalyThoracic Surgery Unit, Careggi University Hospital, Largo Brambilla, 1, 50134 Florence, ItalyDepartment of Biology and Biochemistry, University of Bath, Bath BA2 7AY, UKDepartment of Health Sciences, Section of Clinical Pharmacology and Oncology, University of Florence, Viale Pieraccini, 6, 50139 Florence, ItalyThe treatment of patients affected by non-small cell lung cancer (NSCLC) has been revolutionised by the discovery of druggable mutations. ROS1 (c-ros oncogene) is one gene with druggable mutations in NSCLC. ROS1 is currently targeted by several specific tyrosine kinase inhibitors (TKIs), but only two of these, crizotinib and entrectinib, have received Food and Drug Administration (FDA) approval. Crizotinib is a low molecular weight, orally available TKI that inhibits ROS1, MET and ALK and is considered the gold standard first-line treatment with demonstrated significant activity for lung cancers harbouring ROS1 gene rearrangements. However, crizotinib resistance often occurs, making the treatment of ROS1-positive lung cancers more challenging. A great effort has been undertaken to identify a new generation or ROS1 inhibitors. In this review, we briefly introduce the biology and role of ROS1 in lung cancer and discuss the underlying acquired mechanisms of resistance to crizotinib and the promising new agents able to overcome resistance mechanisms and offer alternative efficient therapies.https://www.mdpi.com/2072-6694/12/11/3293lung cancersolid tumourscrizotinibtoxicityTKI inhibitorsresistance mechanisms |
| spellingShingle | Alberto D’Angelo Navid Sobhani Robert Chapman Stefan Bagby Carlotta Bortoletti Mirko Traversini Katia Ferrari Luca Voltolini Jacob Darlow Giandomenico Roviello Focus on ROS1-Positive Non-Small Cell Lung Cancer (NSCLC): Crizotinib, Resistance Mechanisms and the Newer Generation of Targeted Therapies Cancers lung cancer solid tumours crizotinib toxicity TKI inhibitors resistance mechanisms |
| title | Focus on ROS1-Positive Non-Small Cell Lung Cancer (NSCLC): Crizotinib, Resistance Mechanisms and the Newer Generation of Targeted Therapies |
| title_full | Focus on ROS1-Positive Non-Small Cell Lung Cancer (NSCLC): Crizotinib, Resistance Mechanisms and the Newer Generation of Targeted Therapies |
| title_fullStr | Focus on ROS1-Positive Non-Small Cell Lung Cancer (NSCLC): Crizotinib, Resistance Mechanisms and the Newer Generation of Targeted Therapies |
| title_full_unstemmed | Focus on ROS1-Positive Non-Small Cell Lung Cancer (NSCLC): Crizotinib, Resistance Mechanisms and the Newer Generation of Targeted Therapies |
| title_short | Focus on ROS1-Positive Non-Small Cell Lung Cancer (NSCLC): Crizotinib, Resistance Mechanisms and the Newer Generation of Targeted Therapies |
| title_sort | focus on ros1 positive non small cell lung cancer nsclc crizotinib resistance mechanisms and the newer generation of targeted therapies |
| topic | lung cancer solid tumours crizotinib toxicity TKI inhibitors resistance mechanisms |
| url | https://www.mdpi.com/2072-6694/12/11/3293 |
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