TY - JOUR
T1 - Emerging treatment for ALK-positive lung cancer
AU - Sharma, Janaki
AU - Pareek, Vipul
AU - Liu, Huijie
AU - Cheng, Haiying
N1 - Publisher Copyright:
© 2016 Informa UK Limited, trading as Taylor & Francis Group.
PY - 2016/4/2
Y1 - 2016/4/2
N2 - ABSTRACT: Introduction: Lung cancer is associated with poor prognosis and limited benefit from chemotherapy. The treatment of non-small cell lung cancer (NSCLC) has been revolutionized by the discovery of targetable genetic alterations, including the ALK fusion oncogene. Areascovered: Three drugs have been approved for clinical use in ALK-positive patients – crizotinib, ceritinib and alectinib. Unfortunately, treatment resistance inevitably develops. Several mechanisms of acquired resistance are reported. In this review, we will discuss emerging treatment options in ALK-positive advanced NSCLC and strategies to overcome resistance mechanisms, including newer generation of ALK inhibitors, Hsp90 inhibitors and immunotherapy. Expertopinion: Tremendous advances have been made in the treatment of ALK-positive lung cancers, but management hurdles still exist, including universal development of resistance to ALK inhibitors and limited CNS activity. Given that specific treatment strategies target distinct patterns of resistance, re-biopsy at the time of progression appears necessary to optimize management. However, there remain many issues in routine clinical application including the burden placed on the patients by serial biopsies and the risks of repeat invasive procedures. Future studies are needed to validate the usage of non- or minimally invasive tests and to determine the optimal orders of utilizing different ALK inhibitors.
AB - ABSTRACT: Introduction: Lung cancer is associated with poor prognosis and limited benefit from chemotherapy. The treatment of non-small cell lung cancer (NSCLC) has been revolutionized by the discovery of targetable genetic alterations, including the ALK fusion oncogene. Areascovered: Three drugs have been approved for clinical use in ALK-positive patients – crizotinib, ceritinib and alectinib. Unfortunately, treatment resistance inevitably develops. Several mechanisms of acquired resistance are reported. In this review, we will discuss emerging treatment options in ALK-positive advanced NSCLC and strategies to overcome resistance mechanisms, including newer generation of ALK inhibitors, Hsp90 inhibitors and immunotherapy. Expertopinion: Tremendous advances have been made in the treatment of ALK-positive lung cancers, but management hurdles still exist, including universal development of resistance to ALK inhibitors and limited CNS activity. Given that specific treatment strategies target distinct patterns of resistance, re-biopsy at the time of progression appears necessary to optimize management. However, there remain many issues in routine clinical application including the burden placed on the patients by serial biopsies and the risks of repeat invasive procedures. Future studies are needed to validate the usage of non- or minimally invasive tests and to determine the optimal orders of utilizing different ALK inhibitors.
KW - ALK oncogene
KW - Non-small cell lung cancer
KW - resistance mechanisms
KW - targeted therapy
KW - tyrosine kinase inhibitors
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U2 - 10.1080/14728214.2016.1183642
DO - 10.1080/14728214.2016.1183642
M3 - Review article
C2 - 27122312
AN - SCOPUS:84975259868
SN - 1472-8214
VL - 21
SP - 147
EP - 155
JO - Expert Opinion on Emerging Drugs
JF - Expert Opinion on Emerging Drugs
IS - 2
ER -