Suppressor of cytokine signaling-1 gene therapy improves radiosensitivity in esophageal squamous cell carcinoma

• Project/Area Number: 17H06844
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Digestive surgery
• Research Institution: Osaka University
• Principal Investigator: Pak jongsung 大阪大学, 医学部附属病院, 医員 (80804468)
• Project Period (FY): 2017-08-25 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000); Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 食道がん / SOCS1 / 放射線治療 / 治療耐性 / SOCS / 進行食道胃癌 / 放射線 / 遺伝子治療 / 食道癌 / ウイルス治療 / 放射線耐性

Outline of Final Research Achievements

Recent reports show that signal transducer and activator of transcription 3 (STAT3) plays a prominent role in mediating irradiation (IR)-resistance in various cancers. We firstly investigated the association between STAT3 and IR-resistance in esophageal squamous cell carcinoma (ESCC). Strong expression of p-STAT3 were significantly observed in ESCC patients with preoperative CRT, and their prognosis was significantly poor. Also, the expression of p-STAT3 and anti-apoptotic protein, such as Mcl-1 and survivin was strongly induced after IR. Moreover, ESCC cells with stably STAT3 high expression acquired resistance to IR compared to parent and mock cell. Next, we investigated whether SOCS1 gene therapy using adenovirus (AdSOCS1) improves radiosensitivity in ESCC. Combination radiotherapy with AdSOCS1 showed better growth inhibitory effect and reduced colony forming ability compared to each monotherapy.

Academic Significance and Societal Importance of the Research Achievements

難治癌である食道癌に対する放射線治療耐性のメカニズムの解明ならびにその克服についての研究を行った。本研究成果は、食道癌放射線治療の併用療法の可能性を示唆するものであり、今後の臨床応用が期待される結果である。現在SOCS-1アデノウイルスベクターによる遺伝子治療は、ヒトへの臨床応用化に向けて治験準備中であり、実臨床につながる成果と考える。

Research Products

• [Journal Article] SOCS1 gene therapy has antitumor effects in imatinib-resistant gastrointestinal stromal tumor cells through FAK/PI3K signaling. (2018)
  • Author(s): Sugase T, Takahashi T, Serada S, Fujimoto M, Ohkawara T, Hiramatsu K, Nishida T, Hirota S, Saito Y, Tanaka K, Miyazaki Y, Makino T, Kurokawa Y, Yamasaki M, Nakajima K, Hanasaki K, Kishimoto T, Mori M, Doki Y, Naka T.
  • Journal Title: Gastric Cancer. Volume: epub Issue: 6 Pages: 968-976
  • DOI: 10.1007/s10120-018-0822-1
  • NAID: 40021694606
  • Peer Reviewed / Open Access