title: Ceritinib for the treatment of non-small cell lung cancer.
abstract: Non-small cell lung cancer (NSCLC) represents the paradigm of personalized treatment in human cancer. Several oncogenic alterations with druggable potential have been identified, with ALK rearrangements representing one of the newest and most appealing. Crizotinib is now recognized as the standard of care in chemotherapy-pretreated ALK-positive NSCLC due to the positive results of a recently published trial. Unfortunately, no patient exposed to crizotinib can be cured, and after a median time of 1 year, resistance inevitably occurs. Overcoming resistance is the major challenge in clinical oncology and many molecules are currently under evaluation, including ceritinib (LDK-378). Ceritinib is an oral, potent, second-generation ALK inhibitor recently approved by the U.S. Food and Drug Administration. Preclinical data showed impressive antitumor activity against crizotinib-resistant clones, and based on available data, ceritinib could represent a suitable option in crizotinib-resistant NSCLC.
authors.affiliation: Medical Oncology Department, Istituto Toscano Tumori, Ospedale Civile, Livorno, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Landi
authors.affiliation: Medical Oncology Department, Istituto Toscano Tumori, Ospedale Civile, Livorno, Italy. f.cappuzzo@gmail.com.
authors.forename: F
authors.initials: F
authors.lastname: Cappuzzo
mesh_terms: D000077548:Anaplastic Lymphoma Kinase; D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002986:Clinical Trials as Topic; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011743:Pyrimidines / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics; D013450:Sulfones / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D011743:Pyrimidines; D013450:Sulfones; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases; C586847:ceritinib
keywords: ALK-positive NSCLC; Antitumor activity; Ceritinib; LDK-378; Non-small cell lung cancer