title: The EphB4 receptor tyrosine kinase promotes lung cancer growth: a potential novel therapeutic target.
abstract: Despite progress in locoregional and systemic therapies, patient survival from lung cancer remains a challenge. Receptor tyrosine kinases are frequently implicated in lung cancer pathogenesis, and some tyrosine kinase inhibition strategies have been effective clinically. The EphB4 receptor tyrosine kinase has recently emerged as a potential target in several other cancers. We sought to systematically study the role of EphB4 in lung cancer. Here, we demonstrate that EphB4 is overexpressed 3-fold in lung tumors compared to paired normal tissues and frequently exhibits gene copy number increases in lung cancer. We also show that overexpression of EphB4 promotes cellular proliferation, colony formation, and motility, while EphB4 inhibition reduces cellular viability in vitro, halts the growth of established tumors in mouse xenograft models when used as a single-target strategy, and causes near-complete regression of established tumors when used in combination with paclitaxel. Taken together, these data suggest an important role for EphB4 as a potential novel therapeutic target in lung cancer. Clinical trials investigating the efficacy of anti-EphB4 therapies as well as combination therapy involving EphB4 inhibition may be warranted.
authors.affiliation: Pritzker School of Medicine, University of Chicago, Chicago, Illinois, USA.
authors.forename: Benjamin D
authors.initials: BD
authors.lastname: Ferguson
authors.forename: Ren
authors.initials: R
authors.lastname: Liu
authors.forename: Cleo E
authors.initials: CE
authors.lastname: Rolle
authors.forename: Yi-Hung Carol
authors.initials: YH
authors.lastname: Tan
authors.forename: Valery
authors.initials: V
authors.lastname: Krasnoperov
authors.forename: Rajani
authors.initials: R
authors.lastname: Kanteti
authors.forename: Maria S
authors.initials: MS
authors.lastname: Tretiakova
authors.forename: Gustavo M
authors.initials: GM
authors.lastname: Cervantes
authors.forename: Rifat
authors.initials: R
authors.lastname: Hasina
authors.forename: Robyn D
authors.initials: RD
authors.lastname: Hseu
authors.forename: A John
authors.initials: AJ
authors.lastname: Iafrate
authors.forename: Theodore
authors.initials: T
authors.lastname: Karrison
authors.forename: Mark K
authors.initials: MK
authors.lastname: Ferguson
authors.forename: Aliya N
authors.initials: AN
authors.lastname: Husain
authors.forename: Leonardo
authors.initials: L
authors.lastname: Faoro
authors.forename: Everett E
authors.initials: EE
authors.lastname: Vokes
authors.forename: Parkash S
authors.initials: PS
authors.lastname: Gill
authors.forename: Ravi
authors.initials: R
authors.lastname: Salgia
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001344:Autopsy; D002277:Carcinoma / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics / Q000401:mortality; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D002470:Cell Survival; D004357:Drug Synergism; D018628:Gene Dosage; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics / Q000401:mortality; D051379:Mice; D017239:Paclitaxel / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D036224:Receptor, EphB4 / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D016019:Survival Analysis; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D034741:RNA, Small Interfering; D036224:Receptor, EphB4; D017239:Paclitaxel