title: Tropomyosin-related kinase B inhibitor has potential for tumor regression and relapse prevention in pulmonary large cell neuroendocrine carcinoma.
abstract: Large cell neuroendocrine carcinoma (LCNEC) has an especially poor prognosis, and an effective therapeutic strategy has yet to be established. We have previously shown that the expressions of tropomyosin-related kinase B (TRKB) and brain-derived neurotrophic factor (BDNF) are high in LCNEC and that TRKB/BDNF signaling is involved in the proliferation, tumorigenesis, and invasive nature of LCNEC. Therefore, TRKB/BDNF signaling may offer a potential therapeutic target for LCNEC treatment. In the present study, we evaluated whether the TRKB tyrosine kinase inhibitor, k252a, has effects on tumor regression and relapse prevention on LCNEC, using a murine xenograft model. The LCNEC cell line and NCI-H810 cells were subcutaneously implanted into the flanks or intrathoracically injected into the bilateral pleural cavities of BALB/c nude mice. k252a significantly inhibited tumor volume, expression of matrix metalloproteinases and the formation of pleural dissemination by LCNEC. These results suggest that k252a has potential for tumor regression and relapse prevention in LCNEC. Since many patients with LCNEC suffer through the use of ineffective therapeutic strategies, a clinical trial using the TRKB inhibitor for LCNEC is urgently required.
authors.affiliation: Department of Cancer Therapy and Research, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. ohnishi@surg1.med.kyushu-u.ac.jp.
authors.forename: Seiichi
authors.initials: S
authors.lastname: Odate
authors.forename: Hideya
authors.initials: H
authors.lastname: Onishi
authors.forename: Katsuya
authors.initials: K
authors.lastname: Nakamura
authors.forename: Masayuki
authors.initials: M
authors.lastname: Kojima
authors.forename: Akihiko
authors.initials: A
authors.lastname: Uchiyama
authors.forename: Masato
authors.initials: M
authors.lastname: Kato
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Katano
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002227:Carbazoles / Q000494:pharmacology*; D018287:Carcinoma, Large Cell / Q000201:enzymology / Q000473:pathology*; D018278:Carcinoma, Neuroendocrine / Q000201:enzymology / Q000473:pathology*; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D026121:Indole Alkaloids / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000201:enzymology / Q000473:pathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011494:Protein Kinases / Q000187:drug effects*; D012008:Recurrence
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D002227:Carbazoles; D026121:Indole Alkaloids; D047428:Protein Kinase Inhibitors; C049985:staurosporine aglycone; D011494:Protein Kinases; C041311:tropomyosin kinase
keywords: BDNF; Large cell neuroendocrine carcinoma; TRKB; invasion; lung cancer; tumorigenicity