The identification of molecular markers associated with resistance for molecular targeted agents in GIST

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K10463
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General surgery
• Research Institution: Kumamoto University
• Principal Investigator: IWATSUKI Masaaki 熊本大学, 大学院生命科学研究部(医), 助教 (50452777)
• Co-Investigator(Kenkyū-buntansha): 馬場 祥史 熊本大学, 医学部附属病院, 特任講師 (20599708) ; 吉田 直矢 熊本大学, 医学部附属病院, 特任准教授 (60467983)
• Research Collaborator: Ajani Jaffer A.
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: GIST / リスク分類 / FBXW7 / 術後補助療法

Outline of Final Research Achievements

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the gastrointestinal tract. Surgical resection with negative margin is mainstay of treatment that can offer a permanent cure for primary GIST. However, approximately 50% patients received complete resection subsequently experience recurrence after surgery. The success of imatinib, tyrosine kinase inhibitor in recurrent or metastatic disease setting makes it possible for high-risk patients to adapt to adjuvant therapy after curative surgery. Although these clinical valuables such as mitotic count, primary location and size are developed to predict the recurrence risk, few reliable prognostic molecular biomarkers in GIST have been established. We demonstrated that FBXW7 expression in GIST is an independent predictive marker for RFS by multivariate analysis. FBXW7 may be one of reliable marker for patient selection for adjuvant therapy beside conventional risk stratification in clinical setting.

Free Research Field

消化管外科学　腫瘍外科学　分子腫瘍学

Academic Significance and Societal Importance of the Research Achievements

GISTにおいて再発高リスク群には、イマチニブの術後補助療法が推奨されている。薬物による有害事象などを踏まえると、真に補助療法が必要とされる症例の選択を行うことができる分子生物学的マーカーは重要である。FBXW7は中・高リスク群においても、その低発現はさらに予後不良であり、細胞株を用いた実験でも低発現がGIST細胞株の悪性度を増加させたことから、今後、臨床的に補助療法の患者選択に有用なマーカーとして期待できる。