title: BIIB021, a novel Hsp90 inhibitor, sensitizes esophageal squamous cell carcinoma to radiation.
abstract: BIIB021 is a novel, orally available inhibitor of heat shock protein 90 (Hsp90) that is currently in phase I/II clinical trials. BIIB021 induces the apoptosis of various types of tumor cells in vitro and in vivo. The aim of this study is to investigate the effect of BIIB021 on the radiosensitivity of esophageal squamous cell carcinoma (ESCC). The results indicated that BIIB021 exhibited strong antitumor activity in ESCC cell lines, either as a single agent or in combination with radiation. BIIB021 significantly downregulated radioresistant proteins including EGFR, Akt, Raf-1 of ESCC cell lines, increased apoptotic cells and enhanced G2 arrest that is more radiosensitive cell cycle phase. These results suggest that this synthetic Hsp90 inhibitor simultaneously affects multiple pathways involved in tumor development and progression in the ESCC setting and may represent a better strategy for the treatment of ESCC patients, either as a monotherapy or a radiosensitizer.
authors.affiliation: Department of Radiation Oncology, Qilu Hospital of Shandong University, Jinan 250012, China.
authors.forename: Xin-Tong
authors.initials: XT
authors.lastname: Wang
authors.affiliation: Department of Radiation Oncology, Qilu Hospital of Shandong University, Jinan 250012, China.
authors.forename: Ci-Hang
authors.initials: CH
authors.lastname: Bao
authors.affiliation: Department of Radiation Oncology, Qilu Hospital of Shandong University, Jinan 250012, China.
authors.forename: Yi-Bin
authors.initials: YB
authors.lastname: Jia
authors.affiliation: Department of Radiation Oncology, Qilu Hospital of Shandong University, Jinan 250012, China.
authors.forename: Nana
authors.initials: N
authors.lastname: Wang
authors.affiliation: Department of Radiation Oncology, Cancer Hospital, General Hospital of Ningxia Medical University, Yinchuan 750000, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Ma
authors.affiliation: Medical Imaging, Shandong Medical College, Jinan 250002, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Liu
authors.affiliation: Department of Radiation Oncology, Qilu Hospital of Shandong University, Jinan 250012, China.
authors.forename: Cong
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Radiation Oncology, Qilu Hospital of Shandong University, Jinan 250012, China.
authors.forename: Jian-Bo
authors.initials: JB
authors.lastname: Wang
authors.affiliation: Department of Radiation Oncology, Qilu Hospital of Shandong University, Jinan 250012, China.
authors.forename: Qing-Xu
authors.initials: QX
authors.lastname: Song
authors.affiliation: Department of Radiation Oncology, Qilu Hospital of Shandong University, Jinan 250012, China. Electronic address: qlcyf1965@126.com.
authors.forename: Yu-Feng
authors.initials: YF
authors.lastname: Cheng
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives; D017209:Apoptosis / Q000528:radiation effects; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D004938:Esophageal Neoplasms / Q000378:metabolism* / Q000473:pathology*; D059565:G2 Phase Cell Cycle Checkpoints / Q000528:radiation effects*; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors*; D006801:Humans; D009363:Neoplasm Proteins / Q000378:metabolism*; D011725:Pyridines; D011836:Radiation Tolerance / Q000187:drug effects; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology
chemical_list: C521963:6-chloro-9-(4-methoxy-3,5-dimethylpyridin-2-ylmethyl)-9H-purin-2-ylamine; D018841:HSP90 Heat-Shock Proteins; D009363:Neoplasm Proteins; D011725:Pyridines; D011838:Radiation-Sensitizing Agents; D000225:Adenine
keywords: BIIB021; Esophageal squamous cell carcinoma; Hsp90; Hsp90 inhibitor; Radiosensitivity