IRCCS MultiMedica, Science and Technology Pole, Via Fantoli 16/15, Milan 20138, Italy. adriana.albini@ multimedica.it
Nat Rev Clin Oncol. 2012 Sep;9(9):498-509. doi: 10.1038/nrclinonc.2012.120. Epub 2012 Jul 31.
Healthy individuals can harbour microscopic tumours and dysplastic foci in different organs in an undetectable and asymptomatic state for many years. These lesions do not progress in the absence of angiogenesis or inflammation. Targeting both processes before clinical manifestation can prevent tumour growth and progression. Angioprevention is a chemoprevention approach that interrupts the formation of new blood vessels when tumour cell foci are in an indolent state. Many efficacious chemopreventive drugs function by preventing angiogenesis in the tumour microenvironment. Blocking the vascularization of incipient tumours should maintain a dormancy state such that neoplasia or cancer exist without disease. The current limitations of antiangiogenic cancer therapy may well be related to the use of antiangiogenic agents too late in the disease course. In this Review, we suggest mechanisms and strategies for using antiangiogenesis agents in a safe, preventive clinical angioprevention setting, proposing different levels of clinical angioprevention according to risk, and indicate potential drugs to be employed at these levels. Finally, angioprevention may go well beyond cancer in the prevention of a range of chronic disorders where angiogenesis is crucial, including different forms of inflammatory or autoimmune diseases, ocular disorders, and neurodegeneration.
健康个体在无症状状态下可多年携带处于不可检测的微小肿瘤和异型增生灶于不同器官中。在不存在血管生成或炎症的情况下,这些病变不会进展。在临床表现出现之前针对这两个过程进行靶向治疗可以预防肿瘤生长和进展。血管预防是一种化学预防方法,当肿瘤细胞灶处于惰性状态时,它会中断新血管的形成。许多有效的化学预防药物通过阻止肿瘤微环境中的血管生成来发挥作用。阻断早期肿瘤的血管生成应该维持休眠状态,使肿瘤或癌症存在而不发生疾病。目前抗血管生成癌症治疗的局限性可能与在疾病过程中太晚使用抗血管生成药物有关。在这篇综述中,我们提出了在安全的、预防性的临床血管预防环境中使用抗血管生成药物的机制和策略,根据风险提出了不同水平的临床血管预防,并指出了在这些水平上可使用的潜在药物。最后,血管预防可能不仅限于癌症,还可以预防一系列需要血管生成的慢性疾病,包括各种形式的炎症或自身免疫性疾病、眼部疾病和神经退行性疾病。