Title
ALK and crizotinib : after the honeymoon... what else? Resistance mechanisms and new therapies to overcome itALK and crizotinib : after the honeymoon... what else? Resistance mechanisms and new therapies to overcome it
Author
Faculty/Department
Faculty of Medicine and Health Sciences
Research group
Antwerp Surgical Training, Anatomy and Research Centre (ASTARC)
Laboratory Experimental Medicine and Pediatrics (LEMP)
Molecular Imaging, Pathology, Radiotherapy & Oncology (MIPRO)
Publication type
article
Publication
Subject
Human medicine
Source (journal)
Translational lung cancer research. - -
Volume/pages
3(2014):4, p. 250-261
ISSN
2218-6751
Carrier
E
Target language
English (eng)
Full text (Publishers DOI)
Affiliation
University of Antwerp
Abstract
The last few decades have witnessed a silent revolution in the war against NSCLC, thanks to the discovery of oncogenic drivers and the subsequent development of targeted therapies. The discovery of the EML4-ALK fusion gene in a subgroup of patients with NSCLC and the subsequent clinical development of crizotinib has been an amazing success story in lung cancer translational-research, and its accelerated approval [only four years from the discovery of ALK rearrangement in NSCLC to the approval by the Food and Drug Administration (FDA)] marked the beginning of the new decade of targeted therapy. However, common to all targeted therapies, despite an initial benefit, patients inevitably experience tumor progression, due to the development of resistance. Several molecular mechanisms are responsible for acquired resistance, such as secondary mutations of ALK kinase domain or amplification of ALK fusion gene, or the activation of other oncogenic drivers, which may cause resistance independently of ALK genetic alterations. Pre-clinical data and early clinical trials showed the promising efficacy of a new class of ALK-inhibitors in overcoming acquired resistance. The inhibition of the molecular chaperone, HSP90, represents another promising strategy to overcome crizotinib resistance in ALK-rearranged NSCLC. Several molecules are currently under investigation in order to establish their specific role in the treatment of ALK-rearranged NSCLC.
E-info
https://repository.uantwerpen.be/docman/iruaauth/bb30b9/acbac55326c.pdf
Handle