Abstract:
INTRODUCTION:Crizotinib is a first-in-class ALK tyrosine kinase inhibitor (TKI), which has proven its superiority over standard platinum-based chemotherapy for the first-line therapy of ALK-rearranged non-small cell lung cancer (NSCLC) patients. The development of acquired resistance to crizotinib represents an ongoing challenge with the central nervous system being one of the most common sites of relapse. Ceritinib and alectinib are approved second-generation ALK TKIs. Several novel ALK inhibitors, more potent and with different selectivity compared to crizotinib, are currently in development. Areas covered: This review will focus on new ALK inhibitors, currently in phase 1 or 2 clinical studies. We will also comment on the mechanisms of resistance to ALK inhibition and the strategies to delay or overcome resistance. Expert opinion: The therapeutic management of ALK-rearranged NSCLC has been greatly improved. Next-generation ALK inhibitors have shown differential potency against ALK rearrangements and ALK resistance mutations. The molecular profile of the tumor at the time of disease progression to crizotinib is crucial for the sequencing of novel ALK TKIs. Ongoing clinical studies will address key issues, including the optimal therapeutic algorithm and whether combinational approaches are more effective than single ALK inhibition for the outcome of ALK-rearranged NSCLC patients.
journal_name
Expert Opin Investig Drugsjournal_title
Expert opinion on investigational drugsauthors
Karachaliou N,Santarpia M,Gonzalez Cao M,Teixido C,Sosa AE,Berenguer J,Rodriguez Capote A,Altavilla G,Rosell Rdoi
10.1080/13543784.2017.1324572subject
Has Abstractpub_date
2017-06-01 00:00:00pages
713-722issue
6eissn
1354-3784issn
1744-7658journal_volume
26pub_type
杂志文章,评审abstract:INTRODUCTION:Oxidative stress toxicity (OST) has been implicated in almost all pathological conditions. Despite the widespread use of natural antioxidants, no pharmaceutical antioxidants have yet been developed or prescribed in medical practise. Antioxidant drugs such as Deferiprone and N-acetylcysteine can target esse...
journal_title:Expert opinion on investigational drugs
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journal_title:Expert opinion on investigational drugs
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