肿瘤血管异常化的基础研究与临床应用进展

Progress in basic research and clinical applications of tumor vascular normalization

肿瘤病理性血管的形成可介导缺氧和高渗漏的肿瘤微环境,进而促进肿瘤复发转移、免疫抑制及药物抵抗等诸多肿瘤恶性生物学行为的发生。在肿瘤发生发展的过程中,微环境中的促血管生成因子如血管内皮生长因子(VEGF)和血管生成素(Ang)等被大量释放,进而刺激周围正常血管的增生和突破,形成比正常血管更脆弱、更不稳定以及更容易出血和渗漏的血管网络从而促进肿瘤的生长和扩散。因此,了解和干预肿瘤异常血管生成的机制,可为肿瘤的治疗提供新的思路和方法。虽然通过阻断肿瘤血管形成从而减少肿瘤血供和营养的抗血管生成疗法在肿瘤治疗中已取得一定成功,但适用肿瘤类型的局限性及其可能存在的副反应和耐药性一定程度上限制了临床应用的普适性。研究结果表明,通过改善肿瘤血管的结构和功能可以增加氧气和药物的输送效率以及增加免疫细胞浸润,这种促进血管的修复和正常化的策略是当前肿瘤研究和临床治疗中的热点。

The formation of pathological vessels in tumors can mediate a hypoxic and highly permeable tumor microenvironment;thereby promoting the occurrence of various malignant biological behaviors of tumors;such as recurrence;metastasis;immune suppression;and drug resistance.During the development of tumors;angiogenic factors in the microenvironment;such as vascular endothelial growth factor(VEGF)and angiopoietin(Ang);are released in large quantities.These factors stimulate the proliferation and breakthrough of surrounding normal vessels;forming a vascular network that is more fragile;unstable;and prone to bleeding and leakage than normal vessels;thus promoting tumor growth and spread.Therefore;understanding and intervening in the mechanisms of abnormal tumor angiogenesis can provide new ideas and methods for tumor treatment.Although anti-angiogenic therapy;which blocks tumor vessel formation to reduce tumor blood supply and nutrition;has achieved certain success in tumor treatment;the limitations of applicable tumor types and potential side effects and drug resistance have extent somewhat restricted its universal clinical application.Research results show that improving the structure and function of tumor vessels can increase the efficiency of oxygen and drug delivery and enhance immune cell infiltration.This strategy of promoting vascular repair and normalization is currently a hot topic in tumor research and clinical treatment.