Development of a new therapeutic agent for neuroblastoma using platinum complex-bound PI polyamide

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K18043
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55010:General surgery and pediatric surgery-related
• Research Institution: Nihon University
• Principal Investigator: UEKUSA Shota 日本大学, 医学部, 研究医員 (70746338)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 神経芽腫 / PIポリアミド

Outline of Final Research Achievements

Cisplatin is known to have a radiosensitizing effect. PI polyamide binds to nuclear DNA in a sequence-specific manner. By using PI polyamide to efficiently induce an antitumor drug into the nucleus of tumor cells, which is the field of antitumor action of platinum preparations such as cisplatin, it is possible to obtain a stronger antitumor effect.
Taking advantage of the high nuclear translocation of PI polyamide targeting non-specific gene sequences, cisplatin-like platinum complex and PI polyamide compound　(PIP-Pt) were bound was added to a neuroblastoma cell line. The radiosensitizing effect and antitumor effect were examined. As a result, the radiosensitizing effect was confirmed in the PIP-Pt-added group.

Free Research Field

小児外科

Academic Significance and Societal Importance of the Research Achievements

本研究は、いまだ予後不良である神経芽腫高リスク群患者に対しての新規治療薬剤の開発を目的とする。今回開発するPIP-Ptは低用量でcisplatinと同等以上の治療効果が望める可能性があることから、抗腫瘍薬の副作用を減じる効果が見込まれる。また、本研究では神経芽腫に対するMYCN遺伝子を標的としたが、横紋筋肉腫におけるPAX3-FOXO1遺伝子等、腫瘍特異的に発現している遺伝子を標的としたPIポリアミドを用いて同様の化合物を作成することで、神経芽腫以外の様々な悪性腫瘍に対する新規抗腫瘍薬の開発へと発展することが期待され、学術的、臨床的に大きな意義を持つ。