Elucidation of epigenetic mechanisms of treatment resistance in prostate cancer through AR dependency

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K16727
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56030:Urology-related
• Research Institution: Chiba University
• Principal Investigator: Sato Hiroaki 千葉大学, 医学部附属病院, 助教 (50813250)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 前立腺癌 / がんエピゲノム / 去勢抵抗性 / クロマチン構造

Outline of Final Research Achievements

In castration resistant prostate cancer (CRPC), we performed a comprehensive integrated analysis of various cell-lines and patient-derived tissues for each disease state to identify epigenomic information and gene clusters that change in response to the acquisition of treatment resistance. Focusing on open chromatin regions, CRPCs are broadly clustered into two groups, and candidate transcription factors that characterize each group have been extracted, and functional analysis is ongoing. In addition, focusing on three-dimensional chromatin structural alterations, we found that CRPCs are characterized by a compartment shift from inactive to active state, and we identified the KIF18A gene as an important downstream gene.

Free Research Field

泌尿器悪性腫瘍

Academic Significance and Societal Importance of the Research Achievements

前立腺癌は本邦においても欧米諸国においても男性罹患率上位の重要疾患であり、その治療抵抗性病態である去勢抵抗性前立腺癌に対する新規治療戦略の開発が望まれている。我々は前立腺癌の治療抵抗性獲得の分子機構について、エピゲノムの観点から解析を行なっている。自施設と公共データベースを用いた網羅的統合解析を行なっており、エピゲノムの観点からグローバルな新規知見が得られた点で、学術的意義が高いと考えられる。社会的に克服すべき治療抵抗性病態である去勢抵抗性前立腺癌に対する臨床応用へと繋がる、大きな社会的意義を有していると考える。