title: W'ALK' Into the Next Stage.
abstract: In 2007, the rearrangement of anaplastic lymphoma kinase (ALK) was identified to be associated with the pathogenesis of a subset of patients with non-small-cell lung cancer (NSCLC). Surprisingly, approximately 4 years after the discovery of ALK rearrangement in lung cancer, the first-in-class ALK inhibitor (ALKi), crizotinib, was approved for metastatic ALK-rearranged NSCLC by the US Food and Drug Administration. Subsequently, next-generation ALKis, such as alectinib and ceritinib, have been developed, and some of them have been applied in the clinical setting. Furthermore, various resistance mechanisms against ALKis have been gradually elucidated, and treatment strategies according to such resistance have been proposed. In addition, novel ALKis exhibit good antitumor efficacy for brain metastases. Thus, we now know much about ALK-rearranged NSCLC; however, is it enough? Several concerns, such as the optimal sequence of ALKis, significance of antiangiogenic therapy, immune checkpoint therapy, and cytotoxic chemotherapy in ALK-rearranged NSCLC, should be clearly addressed, which would lead to the establishment of optimal treatment strategies and a more prolonged survival in patients with ALK rearrangement. Thus, we should w'ALK' into the next stage.
authors.affiliation: Department of Thoracic Oncology, National Kyushu Cancer Center, Fukuoka, Japan; Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. Electronic address: gouji104kawa@gmail.com.
authors.forename: Gouji
authors.initials: G
authors.lastname: Toyokawa
authors.affiliation: Department of Thoracic Oncology, National Kyushu Cancer Center, Fukuoka, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Seto
authors.affiliation: Department of Thoracic Oncology, National Kyushu Cancer Center, Fukuoka, Japan.
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Takenoyama
authors.affiliation: Department of Thoracic Oncology, National Kyushu Cancer Center, Fukuoka, Japan.
authors.forename: Yukito
authors.initials: Y
authors.lastname: Ichinose
mesh_terms: D000077548:Anaplastic Lymphoma Kinase; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D015321:Gene Rearrangement; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*
chemical_list: D047428:Protein Kinase Inhibitors; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases
keywords: Anaplastic lymphoma kinase (ALK); Antiangiogenic therapy; Cytotoxic chemotherapy; Immune checkpoint therapy; Sequential therapy with ALK inhibitors