Hypoxia Signaling in Cancer: From Basics to Clinical Practice.
Hypoxia Signaling in Cancer: From Basics to Clinical Practice.
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DOI：
10.3389/pore.2021.1609802
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Tímár J
中科院分区：
文献类型：
--
作者：
Sebestyén A;Kopper L;Dankó T;Tímár J
肿瘤缺氧是肿瘤的重要标志之一，它影响基因表达、代谢，并最终影响肿瘤生物学相关过程。癌症缺氧的主要原因是患者的血管形成不足或不适当以及全身缺氧（通常由贫血引起），导致缺氧诱导的转录因子（HIF）的独特形式的遗传重编程。然而，癌基因驱动的信号通路的组成性激活也可能独立于氧供应激活缺氧信号。肿瘤中HIF激活的结果是血管生成表型、新的代谢谱和免疫抑制微环境。肿瘤组织缺氧和诱导的适应机制是肿瘤耐药的两个主要原因。因此，通过现有的抗缺氧剂如抗血管生成剂、抗贫血疗法或特异性信号传导途径抑制剂，将癌症患者的各种治疗方式联合收割机组合似乎是不可避免的。很明显，癌症患者对开发缺氧的靶向疗法以改善各种抗癌治疗方式的功效存在未满足的需求。由于首个同类产品HIF 2 α抑制剂获得批准，该病例已于近期启动。
Cancer hypoxia, recognized as one of the most important hallmarks of cancer, affects gene expression, metabolism and ultimately tumor biology-related processes. Major causes of cancer hypoxia are deficient or inappropriate vascularization and systemic hypoxia of the patient (frequently induced by anemia), leading to a unique form of genetic reprogramming by hypoxia induced transcription factors (HIF). However, constitutive activation of oncogene-driven signaling pathways may also activate hypoxia signaling independently of oxygen supply. The consequences of HIF activation in tumors are the angiogenic phenotype, a novel metabolic profile and the immunosuppressive microenvironment. Cancer hypoxia and the induced adaptation mechanisms are two of the major causes of therapy resistance. Accordingly, it seems inevitable to combine various therapeutic modalities of cancer patients by existing anti-hypoxic agents such as anti-angiogenics, anti-anemia therapies or specific signaling pathway inhibitors. It is evident that there is an unmet need in cancer patients to develop targeted therapies of hypoxia to improve efficacies of various anti-cancer therapeutic modalities. The case has been opened recently due to the approval of the first-in-class HIF2α inhibitor.
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