Cancer Therapeutics and Chemoprevention Group, Department of Pharmaceutical Sciences, College of Pharmacy, Northeast Ohio Medical University, Rootstown, OH 44272, USA.
Curr Cancer Drug Targets. 2012 Nov 1;12(9):1095-118.
Hepatocellular carcinoma (HCC) remains one of the most lethal cancers in the world. Since current treatment options including surgical resection and liver transplantation offer limited therapeutic benefits, there exists a need to evaluate novel therapeutic strategies for the amelioration of HCC. Hepatic tumors are highly vascularized, possessing a rich network of blood vessels and capillaries and there exist an angiogenic component to the tumor growth observed in HCC. Thus, anti-angiogenic therapy has been suggested to possess tremendous therapeutic potential in the treatment of HCC. The process of angiogenesis involves multiple biochemical checkpoints and signaling steps, and thus providing a multitude of opportunities for therapeutic intervention. In this review, we highlight the role of angiogenesis and its use as a therapeutic strategy for HCC. The first part of the article reviews the angiogenic mechanisms with particular emphasis on the multitude of biochemical factors, such as receptors, enzymes and cytokines involved in the complex interplay of new capillary growth. Next, we present the pre-clinical studies which elucidate the anti-angiogenic effects of both dietary and non-dietary agents in animal models of HCC. Of particular interest is the examination of the effects of the antiangiogenic agents on the various angiogenic markers in the hepatic tissue of the animal challenged either with a hepatocarcinogen or xenografted with hepatic neoplastic cells. The review also highlights the clinical investigations carried out in HCC patients to evaluate the therapeutic potential of pharmacological agents with proven anti-angiogenic properties. Finally, the future directions as well as the benefits and potential challenges involved in the use of antiangiogenic pharmacotherapy in the treatment of HCC are also discussed.
肝细胞癌（HCC）仍然是世界上最致命的癌症之一。由于目前的治疗选择，包括手术切除和肝移植，提供的治疗益处有限，因此需要评估新的治疗策略来改善 HCC。肝肿瘤具有高度血管化的特点，拥有丰富的血管网络和毛细血管，并且在 HCC 中观察到的肿瘤生长存在血管生成成分。因此，抗血管生成治疗被认为在治疗 HCC 方面具有巨大的治疗潜力。血管生成的过程涉及多个生化检查点和信号步骤，因此为治疗干预提供了多种机会。在这篇综述中，我们强调了血管生成的作用及其作为 HCC 治疗策略的用途。文章的第一部分回顾了血管生成的机制，特别强调了多种生化因素，如受体、酶和细胞因子，它们在新毛细血管生长的复杂相互作用中发挥作用。接下来，我们介绍了临床前研究，这些研究阐明了饮食和非饮食因素在 HCC 动物模型中抗血管生成作用。特别有趣的是，研究了抗血管生成剂对动物肝组织中各种血管生成标志物的影响，这些动物要么受到肝癌致癌物的挑战，要么移植了肝肿瘤细胞。该综述还强调了在 HCC 患者中进行的临床研究，以评估具有已证明抗血管生成特性的药理制剂的治疗潜力。最后，还讨论了在 HCC 治疗中使用抗血管生成药物治疗的未来方向、益处和潜在挑战。
