Anaplastic lymphoma kinase rearrangement in lung Cancer: Its biological and clinical significance

Toyokawa, Gouji; Seto, Takashi

doi:10.1016/j.resinv.2014.06.005

Cited by 18 publications

(5 citation statements)

References 77 publications

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“…From the current studies, it can be perceived that old age is a risk factor for various cancers and decreases cardiac function ( Shaw et al, 2011 ; Ou et al, 2013 ), but no clinical study has shown sex differences in cardiac disorders caused by ALK-TKIs ( Ou et al, 2013 ; Ou et al, 2016 ). Patients aged 45–64 years (30.08%) also accounted for a high proportion, which may be associated with the high frequency that patients with NSCLC harboring the EML4-ALK fusion gene were observed in relatively younger patients ( Baldi et al, 2014 ; Toyokawa and Seto, 2014 ).…”

Section: Discussionmentioning

confidence: 99%

Anaplastic Lymphoma Kinase Tyrosine Kinase Inhibitor-Associated Cardiotoxicity: A Recent Five-Year Pharmacovigilance Study

et al. 2022

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Background: Clinical trials frequently reported anaplastic lymphoma kinase tyrosine kinase inhibitors (ALK-TKIs) associated with cardiac adverse drug events (AEs) but minimal postmarketing data. We aimed to research real-world cardiac disorders associated with ALK-TKIs based on the Food and Drug Administration Adverse Event Reporting System (FAERS).Methods: Extract reports from the FAERS from the first quarter of 2016 to the second quarter of 2021 were obtained. Data mining of cardiac disorders associated with ALK-TKIs was carried out using disproportionality analysis to determine the clinical characteristics of AEs.Results: In total, 605 cases were screened out. These events were found to be more prevalent in patients ≥45 years (50.74%) and women (50.74%). The onset time of cardiac disorders was variable and concentrated within 2 months, with a median time of 33 days. The outcomes tended to be poor, with 20.93% fatality proportion. Cardiac arrhythmia was a common adverse event of ALK-TKIs, especially bradycardia. Crizotinib and lorlatinib showed positive signals in cardiac disorders, especially in heart failure, and brigatinib presented no signals. The study also found that myocarditis caused by ceritinib and cardiomyopathy caused by lorlatinib may be potential new adverse drug reactions.Conclusion: ALK-TKIs were reported more frequently in cardiotoxicity than other drugs and could often manifest earlier. We also found potential new AE signals in specific drugs and need more clinical studies to confirm. Our study helps fill the safety information of ALK-TKIs in the heart and provides directions for further research.

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Section: Discussionmentioning

confidence: 99%

Anaplastic Lymphoma Kinase Tyrosine Kinase Inhibitor-Associated Cardiotoxicity: A Recent Five-Year Pharmacovigilance Study

et al. 2022

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“…Current diagnostic approaches to detect ALK fusion genes and their results include break-apart fluorescence in situ hybridization (FISH), IHC, and reverse-transcription PCR (RT-PCR) (21). Break-apart FISH has been established in clinical trials as the standard method for confirmation of ALK status (22).…”

Section: Genomic Biomarkers In Nsclcmentioning

confidence: 99%

Lung Cancer Biomarkers

Villalobos

Wistuba

2017

Hematology/Oncology Clinics of North America

205

181

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Synopsis The molecular characterization of lung cancer has considerably changed the classification and treatment of these tumors, becoming an essential component of pathologic diagnosis and oncologic therapy decisions. Through the recognition of novel biomarkers, such as epidermal growth factor receptor mutations and anaplastic lymphoma kinase translocations, it has been possible to identify subsets of patients who benefit from targeted molecular therapies. The success of targeted anticancer therapies and new immunotherapy approaches has created a new paradigm of personalized therapy and has also led to accelerated development of new drugs for lung cancer treatment. This review focuses on clinically relevant cancer biomarkers as targets for therapy, as well as potential new targets for drug development.

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“…In 2007, the chromosomal rearrangement involving the ALK and EML4 (echinoderm microtubule-associated protein like 4) genes was identified in about 5% of NSCLC patients [ 19 ]; the rearrangement is frequently observed in relatively younger patients, non- or light smokers, and those with adenocarcinoma histology without other genetic disorders, such as mutations of the epidermal growth factor receptor (EGFR) gene [ 20 , 21 ]. All 13 fusion variants of EML4-ALK contain exons 20–29 of ALK , which encode the entire intracellular segment of ALK, and 8 different EML4 exons (2, 6, 13, 14, 15, 17, 18, and 20).…”

Section: Introductionmentioning

confidence: 99%

Role and targeting of anaplastic lymphoma kinase in cancer

et al. 2018

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Anaplastic lymphoma kinase (ALK) gene activation is involved in the carcinogenesis process of several human cancers such as anaplastic large cell lymphoma, lung cancer, inflammatory myofibroblastic tumors and neuroblastoma, as a consequence of fusion with other oncogenes (NPM, EML4, TIM, etc) or gene amplification, mutation or protein overexpression.ALK is a transmembrane tyrosine kinase receptor that, upon ligand binding to its extracellular domain, undergoes dimerization and subsequent autophosphorylation of the intracellular kinase domain. When activated in cancer it represents a target for specific inhibitors, such as crizotinib, ceritinib, alectinib etc. which use has demonstrated significant effectiveness in ALK-positive patients, in particular ALK-positive non- small cell lung cancer.Several mechanisms of resistance to these inhibitors have been described and new strategies are underway to overcome the limitations of current ALK inhibitors.

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Anaplastic lymphoma kinase rearrangement in lung Cancer: Its biological and clinical significance

Cited by 18 publications

References 77 publications

Anaplastic Lymphoma Kinase Tyrosine Kinase Inhibitor-Associated Cardiotoxicity: A Recent Five-Year Pharmacovigilance Study

Anaplastic Lymphoma Kinase Tyrosine Kinase Inhibitor-Associated Cardiotoxicity: A Recent Five-Year Pharmacovigilance Study

Lung Cancer Biomarkers

Role and targeting of anaplastic lymphoma kinase in cancer

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