抗血管生成药物改善肿瘤血供及含氧量的机制探讨和应用展望

Mechanism exploration and future prospects of antiangiogenic agents improving tumor blood supply and oxygenation

肿瘤的生长和转移离不开血管,目前抗血管生成药物已广泛应用于一些恶性肿瘤的临床治疗.其原理为使肿瘤血管退化和再生抑制,从而剥夺肿瘤的氧气和营养供给,达到抑制肿瘤生长和转移的效果.临床上,抗血管生成药物与放、化疗方案联合使用能起到协同抗肿瘤的效果,然而放疗和化疗需要依靠血液来输送氧气和药物,理论上血管退化应当是抑制而非增强放、化疗的效果,这与临床事实相矛盾.随着“血管正常化”理论的提出,越来越多的证据显示抗血管生成药物可以在破坏肿瘤血管之前,先使肿瘤血管的整体生理机能正常化,达到改善肿瘤血供、增加组织含氧量的效果.这对于抗血管生成药物的应用,提出了新的观点和挑战.本文针对抗血管生成药物改善肿瘤血液供应和含氧量的机制、相关研究以及应用展望进行综合论述。

The growth and metastasis of tumor is angiogenesis-dependent.Antiangiogenic agents have been clinically used to treat malignant tumors with the mechanisms of regressing tumor vasculature and inhibiting vascular recurrence which restrain tumor growth and metastasis.Clinical evidences indicate that antiangiogenic agents combined with chemotherapy or radiotherapy potentiate the effects of treatment.However,radiation therapy and chemotherapy depend on ample blood flow to the tumor to deliver oxygen and drugs.Theoretically,it is paradoxical with evidences that these therapies work together rather than against each other.＆quot;Vascular normalization＆quot; theory was raised to explain this paradox.And accumulating data show that antiangiogenic agents transiently ＆quot;normalize＆quot; tumor vasculature before causing vascular regression,so that improve tumor blood supply and increase tissue oxygenation.New views and challenges about antiangiogenic agents come out with the discovery of ＆quot;normalization window＆quot;.In this review,we summarized the mechanism,related researches and future prospects of antiangiogenic agents improving blood supply and oxygenation.