The Novel and Comprehensive Screening of Genes Resistant to an Anticancer Drug and Radiation in Esophageal Squamous Cell Carcinoma

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K07149
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Tumor diagnostics
• Research Institution: Keio University
• Principal Investigator: Kawakubo Hirofumi 慶應義塾大学, 医学部(信濃町), 准教授 (20286496)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 薬剤耐性 / 放射線耐性 / トランスポゾン / 食道癌 / 網羅的解析 / 5-FU / シスプラチン / 放射線

Outline of Final Research Achievements

Multimodal therapies including surgery, chemotherapy, and radiotherapy are necessary for advanced esophageal cancer. However, patients with resistance to chemo or radiotherapy cannot derive benefit from the therapy but suffer side effects. Therefore, detecting resistant genes and mechanisms is essential for tailoring treatment to improve the prognosis.We used a novel method involving transposons to screen and identify drug-resistant genes and radio-resistant genes. The new gene screening technique was useful for detecting candidate of drug-resistant genes in esophageal squamous cell carcinoma. We identified 37 candidate genes responsible for CDDP resistance in the two cell lines derived from ESCC cells. TRIM16 is one of the candidate of CDDP resistant gene. We confirmed TRIM 16 overexpression cell has CDDP resistant using MTT assay and resistance is decreased by knocking down TRIM 16. We also confirmed TRIM 16 overexpression cell has CDDP resistant in vivo xenograft model.

Free Research Field

食道癌

Academic Significance and Societal Importance of the Research Achievements

現在、食道癌に対する根治的治療法は手術、化学療法、放射線療法を組み合わせた集学的治療が行われている。しかし、化学療法、放射線療法の奏効率は決して高くなく、奏効しない症例にとっては有害事象のみの無駄な治療となる。また、治療の経過中に薬剤耐性が生じることで治療不応性となることが問題である。以上より化学療法および放射線耐性のメカニズムの解明が治療戦略に非常に重要と考えられる。トランスポゾンを用いたシスプラチン、5-FU、放射線耐性遺伝子の新しい網羅的解析により、進行食道癌の新たな治療戦略の開発と治療成績の向上が可能である。