Development of liquid biopsy biomarker for precision neoadjuvant treatment for pancreatic cancer

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K22861
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0901:Oncology and related fields
• Research Institution: Shizuoka Cancer Center Research Institute
• Principal Investigator: Imamura Taisuke 静岡県立静岡がんセンター(研究所), その他部局等, 研究員 (20870489)
• Project Period (FY): 2020-09-11 – 2022-03-31
• Keywords: 膵癌 / リキッドバイオプシー / 予後予測 / 個別化医療

Outline of Final Research Achievements

In the present study, we performed a comprehensive genetic analysis of circulating tumor DNA (ctDNA) using pre-operative plasma samples in resectable pancreatic cancer. As a result, somatic driver mutations were detected in 65% of the cases. The detected driver mutations included not only KRAS, but also TP53, CDKN2A, and SMAD4, which are also recognized as major driver genes. In addition, although detected less frequently, other driver mutations, such as ALK, APC, BRAF, EGFR, GNAS, IDH2, KEAP1, KIT, MAP2K1, MTOR, and NRAS were also found; these included actionable mutations. Cases in which positive driver mutations were detected were found to have significantly earlier recurrence and a poorer prognosis. The present comprehensive genomic profiling of ctDNA may serve as a fundamental resource for the development of precision medicine for pancreatic cancer based on liquid biopsy findings.

Free Research Field

肝胆膵外科　腫瘍生物学

Academic Significance and Societal Importance of the Research Achievements

膵癌における血中遊離DNAの研究は、膵癌の主要な遺伝子異常であるKRAS変異の検出が主に試みられてきた。血中遊離DNAにおけるKRAS変異の同定は膵癌の予後を予測し得ることが報告されている。一方で、KRAS変異を標的とした薬物治療は未だ開発されておらず、薬物療法の指標とはなり得なかった。我々は、410遺伝子を対象として網羅的に遺伝子異常を解析した。これまでと同様に血中のDNA異常の解析は予後予測が可能であることに加えて、低頻度ではあるが薬物治療の指標となる遺伝子異常が検出されることを明らかとした。今回の知見がリキッドバイオプシーを指標とした膵癌の個別化医療の実現に貢献し得るものと考える。