Reprogramming of cell polarity in refractory prostate cancer

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K22822
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0901:Oncology and related fields
• Research Institution: Keio University
• Principal Investigator: HONGO Hiroshi 慶應義塾大学, 医学部(信濃町), 共同研究員 (10626675)
• Project Period (FY): 2020-09-11 – 2022-03-31
• Keywords: 去勢抵抗性前立腺癌 / 微小管ネットワーク / バイオインフォマティクス / 薬剤スクリーニング / 細胞極性

Outline of Final Research Achievements

There are few effective treatments for castration-resistant prostate cancer (CRPC), and although novel anticancer agents such as cabazitaxel have begun to be used in recent years, their prognostic value is limited to a few months. Remodeling of microtubule network and cell polarity in cancer cells has been considered to be involved in carcinogenesis and invasive metastasis of cancer, and recently, it has been suggested that it may also contribute to the mechanism of anticancer drug resistance. In this study, we focused on the finding of microtubule and cell polarity remodeling in anticancer drug-resistant prostate cancer cell lines, and derived novel therapeutic strategies targeting microtubule network and cell polarity regulation mechanisms by screening drugs using bioinformatics.

Free Research Field

前立腺癌

Academic Significance and Societal Importance of the Research Achievements

転移性前立腺癌の治療はホルモン療法が中心となる。ほぼ全ての症例で一時的な寛解が得られるが、数年の内にホルモン抵抗性を獲得し、去勢抵抗性前立腺癌（CRPC）となる。CRPCに有効な治療は少なく、近年新規抗癌剤カバジタキセルも使用されているが、生命予後延長効果は数か月程度と限定的であり、カバジタキセル耐性前立腺癌は極めて予後不良であるため、新規治療戦略の開発は喫緊の課題である。申請者はカバジタキセル耐性前立腺癌の微小管ネットワークリモデリングを見出し、バイオインフォマティクスを応用した薬剤スクリーニングにより微小管ネットワークを標的とした新規薬剤を同定した。