Vascular Normalization to Improve Treatment of COVID-19: Lessons from Treatment of Cancer.
Vascular Normalization to Improve Treatment of COVID-19: Lessons from Treatment of Cancer.
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DOI：
10.1158/1078-0432.ccr-20-4750
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发表时间：
2021-05-15
期刊：
影响因子：
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通讯作者：
Jain RK
中科院分区：
文献类型：
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作者：
Munn LL;Stylianopoulos T;Jain NK;Hardin CC;Khandekar MJ;Jain RK
COVID-19 大流行的巨大影响导致人们采取“全力以赴”的方法来寻找新疗法来改善这种疾病的治疗结果。除了引起严重的呼吸道病变外，SARS-CoV-2 感染（如其他呼吸道病毒感染）还会直接或间接导致脉管系统异常，从而可能导致低氧血症。这些血管效应会导致显着的发病率，并可能导致该疾病的死亡。鉴于脉管系统异常和氧合不良也是实体瘤的标志，癌症治疗的经验教训可能有助于确定可重新用于治疗 COVID-19 的药物。尽管导致 COVID-19 血管异常的机制尚不完全清楚，但在癌症患者中观察到的许多相同的血管生成和血栓形成途径可能存在失调。许多抗癌疗法，包括雄激素剥夺疗法（ADT）和免疫检查点阻断（ICB），除了对肿瘤细胞产生直接影响外，还能导致血管正常化。因此，这些在癌症患者的临床试验中得到广泛探索的疗法可能对 COVID-19 患者的脉管系统产生有益的影响。此外，这些药物可能对病程产生额外的影响，因为一些 ADT 可能会影响病毒进入，而 ICB 可能会加速 T 细胞介导的病毒清除。这些癌症治疗的见解可用于消除 COVID-19 和其他形式的低氧性呼吸衰竭中发现的血管病变。
The dramatic impact of the COVID-19 pandemic has resulted in an “all hands on deck” approach to finding new therapies to improve outcomes in this disease. In addition to causing significant respiratory pathology, infection with SARS-CoV-2 (like infection with other respiratory viruses) directly or indirectly results in abnormal vasculature which may contribute to hypoxemia. These vascular effects cause significant morbidity and may contribute to mortality from the disease. Given that abnormal vasculature and poor oxygenation are also hallmarks of solid tumors, lessons from the treatment of cancer may help identify drugs that can be repurposed to treat COVID-19. Although the mechanisms that result in vascular abnormalities in COVID-19 are not fully understood, it is possible that there is dysregulation of many of the same angiogenic and thrombotic pathways seen in cancer patients. Many anti-cancer therapeutics, including androgen deprivation therapy (ADT) and immune checkpoint blockade (ICB), result in vascular normalization in addition to their direct effects on tumor cells. Therefore, these therapies, which have been extensively explored in clinical trials of cancer patients, may have beneficial effects on the vasculature of COVID-19 patients. Furthermore, these drugs may have additional effects on the disease course, as some ADT may impact viral entry, and ICBs may accelerate T-cell mediated viral clearance. These insights from the treatment of cancer may be leveraged to abrogate the vascular pathologies found in COVID-19 and other forms of hypoxemic respiratory failure.