Abe Riichiro, Fujita Yasuyuki, Yamagishi Sho-ichi, Shimizu Hiroshi
Department of Dermatology, Hokkaido University Graduate School of Medicine, Kita-ku, Sapporo, Japan.
Curr Pharm Des. 2008;14(36):3802-9. doi: 10.2174/138161208786898626.
Pigment epithelium-derived factor (PEDF) has recently been shown to be the most potent inhibitor of angiogenesis in the mammalian eye, and is involved in the pathogenesis of angiogenic eye disease such as proliferative diabetic retinopathy. However, a functional role for PEDF in tumor growth and angiogenesis remains to be determined. Melanoma is one of the most highly invasive and metastatic tumors. Malignant Melanoma is an increasingly common malignancy and also one the most invasive and metastatic tumors, and its mortality rates have been rapidly increasing above those of any other cancer in recent years. Surgical resection and systemic chemotherapy are the main therapeutic strategies for the treatment of malignant melanoma. However, these approaches are insufficiently effective and may be associated with significant adverse effects. Angiogenesis, a process by which new vascular networks are formed from pre-existing capillaries, is required for tumors to grow, invade and metastasize. Tumor vessels are genetically stable, and less likely to accumulate mutations that allow them to develop drug resistance in a rapid manner. Therefore, targeting vasculatures that support tumor growth, rather than cancer cells, is currently considered the most promising approach to malignant melanoma therapy. Now, novel anti-angiogenic agents with tolerable side effects are actually desired for the treatment of patients with malignant melanoma. In this paper, we review the current understanding of anti-angiogenic therapy for malignant melanoma, especially focusing on PEDF, which was recently identified as the most potent endogenous inhibitor of angiogenesis in the mammalian eye.
色素上皮衍生因子（PEDF）最近被证明是哺乳动物眼中最有效的血管生成抑制剂，并参与诸如增殖性糖尿病视网膜病变等血管生成性眼病的发病机制。然而，PEDF在肿瘤生长和血管生成中的功能作用仍有待确定。黑色素瘤是侵袭性和转移性最强的肿瘤之一。恶性黑色素瘤是一种日益常见的恶性肿瘤，也是最具侵袭性和转移性的肿瘤之一，近年来其死亡率一直在迅速上升，超过了任何其他癌症。手术切除和全身化疗是治疗恶性黑色素瘤的主要治疗策略。然而，这些方法效果不够理想，且可能伴有显著的不良反应。血管生成是一个由预先存在的毛细血管形成新血管网络的过程，肿瘤生长、侵袭和转移都需要血管生成。肿瘤血管基因稳定，不太可能积累使它们迅速产生耐药性的突变。因此，目前认为靶向支持肿瘤生长的血管系统而非癌细胞是治疗恶性黑色素瘤最有前景的方法。现在，治疗恶性黑色素瘤患者实际上需要具有可耐受副作用的新型抗血管生成药物。在本文中，我们综述了目前对恶性黑色素瘤抗血管生成治疗的认识，尤其关注最近被确定为哺乳动物眼中最有效的内源性血管生成抑制剂的PEDF。
