前立腺がん治療において断続的断食が抗アンドロゲン療法の効果を向上(Study: In prostate cancer, intermittent fasting is found to enhance efficacy of anti-androgen therapy)

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2025-08-11 バッファロー大学(UB)

バッファロー大学の研究で、断続的断食(隔日断食)が前立腺がんに対する抗アンドロゲン療法(エンザルタミドなど)の効果を高めることが初めて示された。マウスモデルで、断食はがん細胞のアミノ酸量とタンパク質合成を抑え、アンドロゲン受容体の発現とシグナルを低下させ、薬剤感受性を向上させた。現在、ホルモン療法を受ける患者を対象に、断続的断食や植物ベースのカロリー制限の効果を検証する臨床試験が進行中である。栄養介入は補助治療として有望視される。

<関連情報>

カロリー制限は、アンドロゲン受容体の翻訳を阻害することで、前立腺がんにおける抗アンドロゲン療法の有効性を高める Caloric Restriction Enhances the Efficacy of Anti-Androgen Therapy in Prostate Cancer by Inhibiting Androgen Receptor Translation

Ricardo A. Cordova;May Elbanna;Christopher Rupert;Sabrina A. Orsi;Noah R. Sommers;Angela J. Klunk;Li Shen;Jagannath Misra;Jocelyne N. Hanquier;Maria Tsompana;Yanqing Wang;David W. Goodrich;Ronald C. Wek;Luigi Fontana;Kirk A. Staschke;Roberto Pili
Cancer Research  Published:August 08 2025
DOI:https://doi.org/10.1158/0008-5472.CAN-24-1986

Abstract

Epidemiological studies suggest that diet can impact the incidence, progression, and response to treatment in multiple cancers, including prostate cancer (PCa). In this study, we investigated the use of dietary interventions, specifically caloric or protein restriction, in combination with anti-androgen therapy as a treatment for PCa. Caloric restriction through alternate-day fasting (ADF) reduced androgen receptor (AR) expression and signaling. This reduction in AR enhanced the anti-tumor activity of the AR antagonist enzalutamide in multiple mouse models of PCa. Mechanistic studies revealed that nutrient starvation via ADF predominantly decreased AR mRNA translation at the elongation stage due to amino acid limitation. Pharmacological agents that similarly impair translation elongation and promote ribosome collisions mimicked the AR translation reduction observed with ADF. Overall, these findings suggest that amino acid limitation through ADF impairs translation elongation in PCa, to which AR mRNA translation is susceptible, leading to a reduction in AR protein levels and enhancing AR-targeted therapy.

医療・健康
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