An insight into lung cancer: a comprehensive review exploring ALK TKI and mechanisms of resistance
Implementation of precision medicine in lung cancer has benefited from intense research in the past years, developing subsequently an improved quality of life and increased overall survival of the patients. Targeted therapy has become one of the most important therapeutic innovations for the non-sm...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Association of Basic Medical Sciences of Federation of Bosnia and Herzegovina
2022-02-01
|
| Series: | Biomolecules & Biomedicine |
| Subjects: | |
| Online Access: | https://www.bjbms.org/ojs/index.php/bjbms/article/view/5859 |
| _version_ | 1797261334230859776 |
|---|---|
| author | Adela Patcas Ana Florica Chis Claudia Florentina Militaru Ioana Roxana Bordea Ruxandra Rajnoveanu Ovidiu Florin Coza Reem Hanna Tamas Tiberiu Doina Adina Todea |
| author_facet | Adela Patcas Ana Florica Chis Claudia Florentina Militaru Ioana Roxana Bordea Ruxandra Rajnoveanu Ovidiu Florin Coza Reem Hanna Tamas Tiberiu Doina Adina Todea |
| author_sort | Adela Patcas |
| collection | DOAJ |
| description |
Implementation of precision medicine in lung cancer has benefited from intense research in the past years, developing subsequently an improved quality of life and increased overall survival of the patients. Targeted therapy has become one of the most important therapeutic innovations for the non-small cell lung cancer (NSCLC) category with anaplastic lymphoma kinase (ALK) gene rearrangement. The aim of this review is to provide a through overview of the main molecules of ALK tyrosine kinase inhibitors (TKI) with their general and particular mechanisms of resistance, the main methods of ALK gene detection, each with advantages and limits and the future perspectives currently under research which try to overcome the mechanisms of resistance. We have used two of the most reliable medical databases EMBASE and PubMed to properly select the latest and the most relevant articles for this topic. Encouraged by the promising results, the clinical practice was enriched by the approval of tyrosine kinase inhibitor molecules, three generations being developed, each one with more powerful agents than the previous ones. Unfortunately, the resistance to TKI eventually occurs and it may be induced by several mechanisms, either known or unknown. Crizotinib was the most intensely studied TKI , becoming the first molecule approved into clinical practice and although four other drugs have been broadly used (alectinib, ceritinib, brigatinib and lorlatinib) it seems that even the most recently developed one remains imperfect due to the resistance mutations that developed. There are two types of resistance generally described for the entire class and for the particular drugs, but half of them remain unknown
|
| first_indexed | 2024-04-24T23:39:34Z |
| format | Article |
| id | doaj.art-e774e6b0b14342f4b4e490510f53815d |
| institution | Directory Open Access Journal |
| issn | 2831-0896 2831-090X |
| language | English |
| last_indexed | 2024-04-24T23:39:34Z |
| publishDate | 2022-02-01 |
| publisher | Association of Basic Medical Sciences of Federation of Bosnia and Herzegovina |
| record_format | Article |
| series | Biomolecules & Biomedicine |
| spelling | doaj.art-e774e6b0b14342f4b4e490510f53815d2024-03-15T13:44:00ZengAssociation of Basic Medical Sciences of Federation of Bosnia and HerzegovinaBiomolecules & Biomedicine2831-08962831-090X2022-02-0122110.17305/bjbms.2021.5859An insight into lung cancer: a comprehensive review exploring ALK TKI and mechanisms of resistanceAdela Patcas0https://orcid.org/0000-0001-7026-910XAna Florica Chis1https://orcid.org/0000-0002-5057-7815Claudia Florentina Militaru2Ioana Roxana Bordea3Ruxandra Rajnoveanu4https://orcid.org/0000-0003-0226-1733Ovidiu Florin Coza5https://orcid.org/0000-0002-8865-2913Reem Hanna6https://orcid.org/0000-0003-2882-2156Tamas Tiberiu7https://orcid.org/0000-0002-0341-3754Doina Adina Todea8https://orcid.org/0000-0003-1306-2350Department of Medical Sciences, Pneumology, Faculty of Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj Napoca, RomaniaDepartment of Medical Sciences, Pneumology, Faculty of Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj Napoca, RomaniaDepartment of Pharmacology, Toxicology and Clinical Pharmacology, “Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania Medisprof Cancer Center, Cluj Napoca, Romania Department of Oral Rehabilitation, “Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania Department of Medical Sciences, Pneumology, Faculty of Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj Napoca, RomaniaDepartment of Medical Oncology and Radiotherapy, “ Iuliu Hatieganu ” University of Medicine and Pharmacy, Cluj-Napoca, Romania Institute of Oncology “Prof.Dr.I.Chiricuta”, Cluj Napoca, Romania Department of Surgical Sciences and Integrated Diagnostics, Laser Therapy Centre, University of Genoa, Genoa, Italy Department of Oral Surgery, Dental Institute, King’s College Hospital NHS Foundation Trust, London, United Kingdom Department of Oral and Maxillofacial Surgery, “Iuliu Hatieganu” University of Medicine and Pharmacy Cluj-Napoca, Cluj Napoca, Romania Department of Medical Sciences, Pneumology, Faculty of Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj Napoca, Romania Implementation of precision medicine in lung cancer has benefited from intense research in the past years, developing subsequently an improved quality of life and increased overall survival of the patients. Targeted therapy has become one of the most important therapeutic innovations for the non-small cell lung cancer (NSCLC) category with anaplastic lymphoma kinase (ALK) gene rearrangement. The aim of this review is to provide a through overview of the main molecules of ALK tyrosine kinase inhibitors (TKI) with their general and particular mechanisms of resistance, the main methods of ALK gene detection, each with advantages and limits and the future perspectives currently under research which try to overcome the mechanisms of resistance. We have used two of the most reliable medical databases EMBASE and PubMed to properly select the latest and the most relevant articles for this topic. Encouraged by the promising results, the clinical practice was enriched by the approval of tyrosine kinase inhibitor molecules, three generations being developed, each one with more powerful agents than the previous ones. Unfortunately, the resistance to TKI eventually occurs and it may be induced by several mechanisms, either known or unknown. Crizotinib was the most intensely studied TKI , becoming the first molecule approved into clinical practice and although four other drugs have been broadly used (alectinib, ceritinib, brigatinib and lorlatinib) it seems that even the most recently developed one remains imperfect due to the resistance mutations that developed. There are two types of resistance generally described for the entire class and for the particular drugs, but half of them remain unknown https://www.bjbms.org/ojs/index.php/bjbms/article/view/5859NSCLCanaplastic lymphoma kinaseALKtyrosine kinase inhibitorsTKIresistance mechanisms |
| spellingShingle | Adela Patcas Ana Florica Chis Claudia Florentina Militaru Ioana Roxana Bordea Ruxandra Rajnoveanu Ovidiu Florin Coza Reem Hanna Tamas Tiberiu Doina Adina Todea An insight into lung cancer: a comprehensive review exploring ALK TKI and mechanisms of resistance Biomolecules & Biomedicine NSCLC anaplastic lymphoma kinase ALK tyrosine kinase inhibitors TKI resistance mechanisms |
| title | An insight into lung cancer: a comprehensive review exploring ALK TKI and mechanisms of resistance |
| title_full | An insight into lung cancer: a comprehensive review exploring ALK TKI and mechanisms of resistance |
| title_fullStr | An insight into lung cancer: a comprehensive review exploring ALK TKI and mechanisms of resistance |
| title_full_unstemmed | An insight into lung cancer: a comprehensive review exploring ALK TKI and mechanisms of resistance |
| title_short | An insight into lung cancer: a comprehensive review exploring ALK TKI and mechanisms of resistance |
| title_sort | insight into lung cancer a comprehensive review exploring alk tki and mechanisms of resistance |
| topic | NSCLC anaplastic lymphoma kinase ALK tyrosine kinase inhibitors TKI resistance mechanisms |
| url | https://www.bjbms.org/ojs/index.php/bjbms/article/view/5859 |
| work_keys_str_mv | AT adelapatcas aninsightintolungcanceracomprehensivereviewexploringalktkiandmechanismsofresistance AT anafloricachis aninsightintolungcanceracomprehensivereviewexploringalktkiandmechanismsofresistance AT claudiaflorentinamilitaru aninsightintolungcanceracomprehensivereviewexploringalktkiandmechanismsofresistance AT ioanaroxanabordea aninsightintolungcanceracomprehensivereviewexploringalktkiandmechanismsofresistance AT ruxandrarajnoveanu aninsightintolungcanceracomprehensivereviewexploringalktkiandmechanismsofresistance AT ovidiuflorincoza aninsightintolungcanceracomprehensivereviewexploringalktkiandmechanismsofresistance AT reemhanna aninsightintolungcanceracomprehensivereviewexploringalktkiandmechanismsofresistance AT tamastiberiu aninsightintolungcanceracomprehensivereviewexploringalktkiandmechanismsofresistance AT doinaadinatodea aninsightintolungcanceracomprehensivereviewexploringalktkiandmechanismsofresistance AT adelapatcas insightintolungcanceracomprehensivereviewexploringalktkiandmechanismsofresistance AT anafloricachis insightintolungcanceracomprehensivereviewexploringalktkiandmechanismsofresistance AT claudiaflorentinamilitaru insightintolungcanceracomprehensivereviewexploringalktkiandmechanismsofresistance AT ioanaroxanabordea insightintolungcanceracomprehensivereviewexploringalktkiandmechanismsofresistance AT ruxandrarajnoveanu insightintolungcanceracomprehensivereviewexploringalktkiandmechanismsofresistance AT ovidiuflorincoza insightintolungcanceracomprehensivereviewexploringalktkiandmechanismsofresistance AT reemhanna insightintolungcanceracomprehensivereviewexploringalktkiandmechanismsofresistance AT tamastiberiu insightintolungcanceracomprehensivereviewexploringalktkiandmechanismsofresistance AT doinaadinatodea insightintolungcanceracomprehensivereviewexploringalktkiandmechanismsofresistance |