Emerging treatment for ALK-positive lung cancer.
BACKGROUND
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.


METHODS
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.


CONCLUSIONS
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.
a Division of Medical Oncology , Montefiore Medical Center, Albert Einstein College of Medicine , Bronx , NY , USA.
Janaki
J
Sharma
a Division of Medical Oncology , Montefiore Medical Center, Albert Einstein College of Medicine , Bronx , NY , USA.
Vipul
V
Pareek
a Division of Medical Oncology , Montefiore Medical Center, Albert Einstein College of Medicine , Bronx , NY , USA.
Huijie
H
Liu
a Division of Medical Oncology , Montefiore Medical Center, Albert Einstein College of Medicine , Bronx , NY , USA.
Haiying
H
Cheng
D000077548:Anaplastic Lymphoma Kinase; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D015195:Drug Design; D019008:Drug Resistance, Neoplasm; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics*
D000970:Antineoplastic Agents; D018841:HSP90 Heat-Shock Proteins; D047428:Protein Kinase Inhibitors; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases
ALK oncogene; Non-small cell lung cancer; resistance mechanisms; targeted therapy; tyrosine kinase inhibitors