Bone invasion-targeted chemotherapy with a novel anionic platinum complex (3Pt) for oral squamous cell carcinoma

2019 Fiscal Year Final Research Report

• Project/Area Number: 16K11227
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Otorhinolaryngology
• Research Institution: Kanazawa University
• Principal Investigator: ENDO KAZUHIRA 金沢大学, 附属病院, 助教 (30547154)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Keywords: 頭頸部癌 / シスプラチン / drug delivery system

Outline of Final Research Achievements

Cisplatin (CDDP) is an important drug for chemotherapy in patients with head and neck squamous cell carcinoma. To increase its antitumor effect on bone invasion and reduce toxicity problems, anionic Pt complex (3Pt) has been developed. The present study aimed to characterize the basis of the cytotoxicity of the novel platinum complex 3Pt in comparison with that of CDDP . Both 3Pt and CDDP showed equivalent antitumor effects in vivo. Mice injected with CDDP developed renal cell apoptosis; however, those injected with 3Pt were almost free of renal cell injury. In addition to similar in vivo antitumor effects, 3Pt decreased the volume of bone resorption compared to that with CDDP in a bone invasion model using OSC-19. In conclusion, considering the potential advantages in terms of noticeable antitumor activity on bone invasion and reduced nephrotoxicity, 3Pt represents a significant improvement in the development of bone-targeting platinum drug

Free Research Field

頭頸部腫瘍

Academic Significance and Societal Importance of the Research Achievements

頭頸部癌における化学放射線療法は臓器温存の観点からも手術と並んで重要な標準療法の一つである。分子標的薬、免疫チェックポイント阻害剤など多くの薬剤が開発される現在においてもシスプラチンがキードラックの一つである。しかし骨浸潤に対する抵抗性、多くの有害事象が臨床的に問題となっている。こうした背景からdrug delivery systemの観点から、本研究ではリン酸化イオンを結合したシスプラチン（3Pt)を用いて頭頸部癌における有用性を検証した。今回の基礎研究に基づき特に、骨浸潤した症例での有用性が確認できた。今後は本薬剤のヒトにおける安全性、有効性の検証し頭頸部癌治療におけるブレイクスルーとなる