Epigenetic mechanism of castration resistance prostate cancer in response to tumor microenvironment

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K18133
• 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: Kanesaka Manato 千葉大学, 医学部附属病院, 助教 (60775039)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 去勢抵抗性前立腺癌 / 癌エピゲノム / 低酸素環境

Outline of Final Research Achievements

Castration-resistant prostate cancer is a lethal disease, and one of its main causes is heterogeneity induced by exposure to the tumor microenvironment associated with treatment stress. However, the molecular mechanism is not fully understood. In this study, we focused on the effects of the microenvironment on prostate cancer and the differences in the environmental response, and performed comprehensive epigenomic analysis using prostate cancer cell lines. Our results identified alteration of metabolic profiles after the acquisition of castration resistance, and showed that microenvironment-derived epigenomic changes may influence the acquisition of castration resistance.

Free Research Field

前立腺癌

Academic Significance and Societal Importance of the Research Achievements

去勢抵抗性前立腺癌における腫瘍微小環境によるheterogeneityの変化については十分に解明されておらず、その分子メカニズムやゲノム変異以外のエピゲノム異常機構については未だ不明な点が多い。本研究はその一端を説明するものであり、微小環境への分子応答機構をゲノム変化や遺伝子発現変化より早期に起こるエピゲノム変化に着目した。治療抵抗性獲得のより早期に、さらに既存の治療戦略とは異なる視点から層別化しうる可能性を秘めており、実臨床において適切な個別化医療の展開へ繋がることが期待される。