Zarei Elmira, Zarei Ayda, Omidkhoda Azadeh
Department of Hematology and Blood Banking, School of Allied Medical Sciences, Tehran University of Medical Sciences, Tehran, Iran.
Department of Laboratory Sciences, School of Paramedical Sciences, Shiraz University of Medical Sciences, Shiraz, Iran.
Front Pharmacol. 2025 Apr 15;16:1534686. doi: 10.3389/fphar.2025.1534686. eCollection 2025.
Hematological malignancies are the fifth most prevalent cancer category in developed countries, presenting significant treatment challenges. The side effects of chemotherapy and its non-selective nature have led researchers to explore combination therapies to enhance efficacy and improve patient outcomes. Parthenolide (PTL) emerges as a promising candidate, being the first small molecule identified for its selective action against leukemic stem cells. This article provides an overview of PTL's effects and its potential as a complementary treatment for hematological malignancies. A systematic search in PubMed, Scopus, Embase and Web of Science identified relevant studies using keywords and MeSH terms. Peer-reviewed studies examining PTL's mechanisms and therapeutic potential were included, while non-hematological studies and those lacking rigor were excluded. PTL targets key signaling pathways to combat malignancy, inhibiting NF-κB and signal transducer and STAT3, promoting ROS production, and activating p53. These mechanisms contribute to its effectiveness in treating hematological malignancies. Approaches incorporating PTL or its derivatives show promise in increasing leukemic cell sensitivity to existing therapies and reducing resistance likelihood. Additionally, studies indicate that other drugs can synergistically enhance PTL's ability to eliminate leukemic cells. In conclusion, PTL represents a promising avenue for improving therapeutic outcomes in hematological malignancies, warranting further investigation into its mechanisms and potential in combination therapies.
血液系统恶性肿瘤是发达国家中第五大最常见的癌症类型，带来了重大的治疗挑战。化疗的副作用及其非选择性性质促使研究人员探索联合疗法，以提高疗效并改善患者预后。小白菊内酯（PTL）成为一个有前景的候选药物，是首个被鉴定出对白血病干细胞具有选择性作用的小分子。本文概述了PTL的作用及其作为血液系统恶性肿瘤辅助治疗的潜力。通过在PubMed、Scopus、Embase和科学网中进行系统检索，使用关键词和医学主题词（MeSH）确定了相关研究。纳入了审查PTL机制和治疗潜力的同行评审研究，同时排除了非血液学研究和缺乏严谨性的研究。PTL靶向关键信号通路以对抗恶性肿瘤，抑制核因子κB（NF-κB）和信号转导及转录激活因子3（STAT3），促进活性氧（ROS）生成，并激活p53。这些机制有助于其在治疗血液系统恶性肿瘤方面的有效性。包含PTL或其衍生物的方法在提高白血病细胞对现有疗法的敏感性和降低耐药可能性方面显示出前景。此外，研究表明其他药物可协同增强PTL消除白血病细胞的能力。总之，PTL是改善血液系统恶性肿瘤治疗效果的一个有前景的途径，值得进一步研究其机制以及在联合疗法中的潜力。
