Elucidation of radiation resistance mechanism of oral cancer targeting PARP and creation of new treatment strategy

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K18700
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 57060:Surgical dentistry-related
• Research Institution: Kumamoto University
• Principal Investigator: Sakata Junki 熊本大学, 病院, 医員 (70823326)
• Project Period (FY): 2020-04-01 – 2022-03-31
• Keywords: 口腔癌 / 治療抵抗性 / PARP

Outline of Final Research Achievements

PARP is mainly involved in the repair of DNA single-strand breaks, and olaparib inhibits PARP to prevent the repair of DNA single-strand breaks, leading to cell death. In this study, we investigated the effect of olaparib on oral cancer. As a result, it was shown that the therapeutic effect of cisplatin and radiation may be improved by the combined use of olaparib in oral squamous cell carcinoma. In adenoid cystic carcinoma, it was shown that the combined use of olaparib may improve the therapeutic effect of radiation. As a mechanism for enhancing the therapeutic effect, it is possible that DNA single-strand repair is inhibited by olaparib in DNA damaged by anticancer agents or irradiation, resulting in more lethal DNA damages.

Free Research Field

口腔外科学

Academic Significance and Societal Importance of the Research Achievements

口腔癌において放射線治療との併用による有用性が示されている抗癌剤は限られているのが現状であるが、本研究の結果、オラパリブを放射線治療やシスプラチンのようなDNAに作用する一部の抗癌剤と併用することで治療効果が向上する可能性が示された。PRAPを標的とした治療を応用することにより、口腔癌患者の予後が改善する可能性が示された。