An insight into lung cancer: a comprehensive review exploring ALK TKI and mechanisms of resistance

  • Adela Patcas Department of Medical Sciences, Pneumology, Faculty of Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj Napoca, Romania https://orcid.org/0000-0001-7026-910X
  • Ana Florica Chis Department of Medical Sciences, Pneumology, Faculty of Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj Napoca, Romania https://orcid.org/0000-0002-5057-7815
  • Claudia Florentina Militaru Department of Pharmacology, Toxicology and Clinical Pharmacology, “Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania Medisprof Cancer Center, Cluj Napoca, Romania
  • Ioana Roxana Bordea Department of Oral Rehabilitation, “Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania
  • Ruxandra Rajnoveanu Department of Medical Sciences, Pneumology, Faculty of Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj Napoca, Romania https://orcid.org/0000-0003-0226-1733
  • Ovidiu Florin Coza Department 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 https://orcid.org/0000-0002-8865-2913
  • Reem Hanna 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 https://orcid.org/0000-0003-2882-2156
  • Tamas Tiberiu Department of Oral and Maxillofacial Surgery, “Iuliu Hatieganu” University of Medicine and Pharmacy Cluj-Napoca, Cluj Napoca, Romania https://orcid.org/0000-0002-0341-3754
  • Doina Adina Todea Department of Medical Sciences, Pneumology, Faculty of Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj Napoca, Romania https://orcid.org/0000-0003-1306-2350
Keywords: NSCLC, anaplastic lymphoma kinase, ALK, tyrosine kinase inhibitors, TKI, resistance mechanisms

Abstract

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

 

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Published
2021-05-15
How to Cite
1.
Patcas A, Chis AF, Militaru CF, Bordea IR, Rajnoveanu R, Coza OF, Hanna R, Tiberiu T, Todea DA. An insight into lung cancer: a comprehensive review exploring ALK TKI and mechanisms of resistance. Bosn J of Basic Med Sci [Internet]. 2021May15 [cited 2021Oct.28];. Available from: https://www.bjbms.org/ojs/index.php/bjbms/article/view/5859
Section
Reviews