The role of SMAD4 expression in carcinogenesis and therapeutic resistance of oral cancer

2019 Fiscal Year Final Research Report

• Project/Area Number: 19K21413
• Project/Area Number (Other): 18H06329 (2018)
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund (2019); Single-year Grants (2018)
• Review Section: 0907:Oral science and related fields
• Research Institution: Kumamoto University
• Principal Investigator: Sakata Junki 熊本大学, 病院, 医員 (70823326)
• Project Period (FY): 2018-08-24 – 2020-03-31
• Keywords: 口腔癌 / 治療抵抗性 / SMAD4 / 発癌 / 口腔白板症

Outline of Final Research Achievements

In the present study, we investigated SMAD4 expression status in biopsy specimens from patients with oral squamous cell carcinoma (OSCC) using immunohistochemical analysis and found that the low SMAD4 expression significantly correlates with poor response to preoperative chemoradiotherapy. Furthermore, we demonstrated that SMAD4 is associated with chemoresistance by activating anti-apoptotic effects via overexpression of cIAP2 in OSCC cells. Therefore, our data indicate that SMAD4 could be useful as a therapeutic biomarker of OSCC. Therapies targeting the SMAD4-dependent anti-apoptotic effects combined with chemotherapy could represent a promising new approach for overcoming chemotherapeutic resistance in OSCC, thereby improving the survival rate.

Free Research Field

口腔癌

Academic Significance and Societal Importance of the Research Achievements

口腔扁平上皮癌（OSCC）は口腔癌の80％以上を占める悪性腫瘍であり、近年、OSCCの診断・治療法の選択肢は広がっているが、その5年生存率に大きな改善はみられない。また、わが国での口腔癌および咽頭癌による年間死亡者数は過去15年で約1.5倍に増加しており、その増加傾向の抑制が急務とされる。本研究の成果としてSMAD4が口腔白板症からの癌化予測因子、OSCCの治療効果予測因子および治療標的として応用できる可能性が示唆された。