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首页> 外文期刊>Gene Therapy and Molecular Biology >Cancer therapy by means of irreversible tumorblood flow stasis: Starvation tactics against solidtumors
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Cancer therapy by means of irreversible tumorblood flow stasis: Starvation tactics against solidtumors

机译：通过不可逆的肿瘤血流淤滞进行癌症治疗：针对实体瘤的饥饿策略

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Despite extensive research efforts, effective therapies for advanced cancers have not yet been established, and development of successful treatment strategies remains the most important task in the field of oncology. Three significant problems in conventional chemotherapy using cytotoxic drugs require attention: (i) choosing the most effective drug for individual patients, (ii) delivering a sufficient dose of drug to tumor, and (iii) minimizing severe side effects of anticancer drugs. Because the cancer cells are themselves the direct target of the drugs, these three problems cannot be avoided. We recently showed that AC7700 (currently AVE8062) a derivative of combretastatin A-4, achieved irreversible stasis of tumor blood flow (TBF), thereby causing necrosis of tumor tissue by halting the supply of nutrients. Such effects were unrelated to cancer type, in that they were found for various solid tumors. In this review, we summarize our research on AC7700 and tumor vessels and discuss how AC7700 causes stasis of TBF and why the blood flow does not resume. This technique of attacking tumor by means of blocking TBF largely avoids the three problems typically encountered in conventional cancer chemotherapy that were mentioned above. We propose that such starvation tactics constitute a new therapeutic approach to solid tumors, including refractory cancers which are resistant to conventional cytotoxic drugs and recurrent cancers that have acquired drug resistance.
机译：尽管进行了广泛的研究努力，但尚未建立针对晚期癌症的有效疗法，开发成功的治疗策略仍然是肿瘤学领域最重要的任务。使用细胞毒性药物的常规化学疗法中的三个重要问题需要引起注意：（i）为个别患者选择最有效的药物;（ii）向肿瘤输送足够剂量的药物;（iii）最小化抗癌药物的严重副作用。因为癌细胞本身就是药物的直接靶标，所以这三个问题是无法避免的。我们最近发现，康普他汀A-4的衍生物AC7700（当前为AVE8062）实现了不可逆的肿瘤血流停滞（TBF），从而通过停止营养供应而导致肿瘤组织坏死。这种作用与癌症类型无关，因为它们被发现用于各种实体瘤。在这篇综述中，我们总结了对AC7700和肿瘤血管的研究，并讨论了AC7700如何导致TBF停滞以及为什么血流无法恢复。通过阻断TBF攻击肿瘤的技术很大程度上避免了上述常规癌症化学疗法中通常遇到的三个问题。我们建议这种饥饿策略构成一种针对实体瘤的新治疗方法，包括对常规细胞毒性药物具有耐药性的难治性癌症和已获得耐药性的复发性癌症。

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