急性骨髄性白血病におけるNrf2の標的化:化学抵抗と新興治療戦略におけるその役割に関する更新されたレビュー

Deepthi Maria Mathew¹, Abilash Valsala Gopalakrishnan²

¹Department of Biomedical Sciences, School of Biosciences and Technology, Vellore Institute of Technology, Tamil Nadu, Vellore, 632014, India.

Medical oncology (Northwood, London, England)

|September 1, 2025

まとめ

核因子エリソイド2関連因子2 (Nrf2) の活性化が,急性骨髄性白血病 (AML) の治療抵抗を誘発する. Nrf2を標的とした組み合わせ治療は,AMLの治療結果を改善する可能性があります.

科学分野:

血液学
腫瘍学
分子生物学

背景:

急性骨髄性白血病 (AML) は,治療抵抗性および再発を克服する上で重大な課題を持つ攻撃的な血液がんです.
転写因子核エリソイド2関連因子2 (Nrf2) は細胞生存に重要な役割を果たし,AMLにおける化学抵抗に関与している.
持続的なNrf2活性化は,AMLを含む様々な癌と関連しており,治療目標としての可能性を強調しています.

研究の目的:

Nrf2がAMLにおける治療抵抗に寄与する分子メカニズムの見直し.
Nrf2の活性化経路と現在の治療法の限界を要約する.
Nrf2阻害剤を併用したAML治療の戦略を分析する.

主な方法:

Nrf2の調節,AMLの化学抵抗性におけるその役割,および新たな治療戦略に焦点を当てた文献レビュー.
ミクロRNA (miRNA) のNrf2の調節,ヘム酸素酵素-1 (HO-1) の上調,およびペントースリン酸経路 (PPP) による代謝再プログラムを含む分子機構の分析.
Nrf2 阻害剤との併用療法の可能性と現在の治療制限の評価

主要な成果:

Nrf2の活性化は,しばしば酸化ストレスとKEAP1の無活性化によって引き起こされ,AML細胞の生存と治療抵抗性を促進する.
Nrf2は,miRNAs,HO-1,およびペントースリン酸経路 (PPP) の調節によってAMLの進行に影響を与えます.
現在のAML治療は,無意識に酸化ストレスを誘発し,Nrf2媒介による耐性を引き起こす可能性があります.

結論:

Nrf2はAMLにおける化学抵抗性の重要な媒介であり,重要な細胞プロセスに影響を与える.
Nrf2阻害剤を併用して従来の化学療法や標的治療薬を用いた併用治療は,AMLの耐性を克服する有望な結果を示しています.
AMLの治療プロトコルを最適化するために,組み合わせ戦略のさらなる調査が必要である.

キーワード:

AML について組み合わせ治療薬剤耐性 Nrf2 について酸化ストレス

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