EML4-ALK Fusion Gene in Patients with Lung Carcinoma: Biology, Diagnostics and Targeted Therapy
Authors:
A. Vašíková
Authors‘ workplace:
Centrum molekulární biologie a genové terapie, Interní hematologická a onkologická klinika LF MU a FN Brno
Published in:
Klin Onkol 2012; 25(6): 434-439
Category:
Reviews
Autorka deklaruje, že v souvislosti s předmětem studie nemá žádné komerční zájmy.
Redakční rada potvrzuje, že rukopis práce splnil ICMJE kritéria pro publikace zasílané do bi omedicínských časopisů.
Overview
Targeted therapy currently represents one of possible treatment strategies for lung cancer. High efficacy is achieved by specific inhibition of the target which is abnormally activated in a tumor cell and plays a key role in oncogenesis. EML4-ALK fusion gene, first described five years ago in patients with lung adenocarcinoma, undoubtedly has oncogenic potential and represents a promising candidate for targeted therapy. EML4-ALK fusion occurs due to paracentric inversion in the short arm of chromosome 2 and is detected in 3–5% of patients with non-small cell lung cancer. Moreover, additional fusion partners of ALK gene have been identified: TGF, KIF5B and KLC1. Targeted inhibition of constitutively activated ALK kinase mediated by crizotinib in patients positive for ALK gene rearrangements resulted in remarkable treatment response (57%) with minimal toxicity. Nevertheless, loss of response during crizotinib treatment was reported recently due to development of two resistant mutations (C1156Y and L1196M) within the kinase domain of the fusion protein. Therefore, novel, highly specific inhibitors able to overcome resistance of mutated EML4-ALK are needed. Molecular diagnostics plays an essential role in selection of suitable patients for targeted therapy and offers various methods for detection of ALK gene rearrangements. Identification of tumor-associated genetic changes together with development of novel molecular inhibitors shifts the treatment of oncologic patients towards individualized therapy.
Key words:
EML4-ALK fusion protein – non-small cell lung cancer – molecular diagnostics – molecular targeted therapy – protein kinase inhibitors – crizotinib
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Paediatric clinical oncology Surgery Clinical oncologyArticle was published in
Clinical Oncology
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