Soltani Mojdeh, Zhao Yue, Xia Zhijia, Ganjalikhani Hakemi Mazdak, Bazhin Alexandr V
Department of Immunology, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.
Department of General, Visceral, and Transplant Surgery, Ludwig-Maximilians-University Munich, Munich, Germany.
Front Oncol. 2021 Nov 10;11:767026. doi: 10.3389/fonc.2021.767026. eCollection 2021.
Despite recent advancements in the treatment of hematologic malignancies and the emergence of newer and more sophisticated therapeutic approaches such as immunotherapy, long-term overall survival remains unsatisfactory. Metabolic alteration, as an important hallmark of cancer cells, not only contributes to the malignant transformation of cells, but also promotes tumor progression and metastasis. As an immune-escape mechanism, the metabolic adaptation of the bone marrow microenvironment and leukemic cells is a major player in the suppression of anti-leukemia immune responses. Therefore, metabolic rewiring in leukemia would provide promising opportunities for newer therapeutic interventions. Several therapeutic agents which affect essential bioenergetic pathways in cancer cells including glycolysis, β-oxidation of fatty acids and Krebs cycle, or anabolic pathways such as lipid biosynthesis and pentose phosphate pathway, are being tested in various types of cancers. So far, numerous preclinical or clinical trial studies using such metabolic agents alone or in combination with other remedies such as immunotherapy are in progress and have demonstrated promising outcomes. In this review, we aim to argue the importance of metabolic alterations and bioenergetic pathways in different types of leukemia and their vital roles in disease development. Designing treatments based on targeting leukemic cells vulnerabilities, particularly in nonresponsive leukemia patients, should be warranted.
尽管血液系统恶性肿瘤的治疗最近取得了进展，并且出现了更新、更复杂的治疗方法，如免疫疗法，但长期总体生存率仍然不尽人意。代谢改变作为癌细胞的一个重要标志，不仅有助于细胞的恶性转化，还能促进肿瘤的进展和转移。作为一种免疫逃逸机制，骨髓微环境和白血病细胞的代谢适应是抑制抗白血病免疫反应的主要因素。因此，白血病中的代谢重编程将为新的治疗干预提供有希望的机会。几种影响癌细胞基本生物能量途径（包括糖酵解、脂肪酸β氧化和三羧酸循环）或合成代谢途径（如脂质生物合成和磷酸戊糖途径）的治疗药物正在各类癌症中进行测试。到目前为止，许多单独使用此类代谢药物或与免疫疗法等其他疗法联合使用的临床前或临床试验研究正在进行中，并已显示出有希望的结果。在本综述中，我们旨在论证不同类型白血病中代谢改变和生物能量途径的重要性及其在疾病发展中的关键作用。基于针对白血病细胞脆弱性设计治疗方法，尤其是在无反应的白血病患者中，应该是有必要的。
