Department of Cellular Pathology, Southmead Hospital, Bristol BS10 5NB, UK.
Institute of Biomedical and Clinical Sciences, Medical School, College of Medicine and Health, University of Exeter, Exeter EX12LU, UK.
Int J Mol Sci. 2019 May 31;20(11):2676. doi: 10.3390/ijms20112676.
Prostate cancer is the most commonly diagnosed cancer among men in the Western world. Although localized disease can be effectively treated with established surgical and radiopharmaceutical treatments options, the prognosis of castration-resistant advanced prostate cancer is still disappointing. The objective of this study was to review the role of angiogenesis in prostate cancer and to investigate the effectiveness of anti-angiogenic therapies. A literature search of clinical trials testing the efficacy of anti-angiogenic therapy in prostate cancer was performed using Pubmed. Surrogate markers of angiogenic activity (microvessel density and vascular endothelial growth factor A (VEGF-A) expression) were found to be associated with tumor grade, metastasis, and prognosis. Six randomizedstudies were included in this review: two phase II trials on localized and hormone-sensitive disease ( = 60 and 99 patients) and four phase III trials on castration-resistant refractory disease ( = 873 to 1224 patients). Although the phase II trials showed improved relapse-free survival and stabilisation of the disease, the phase III trials found increased toxicity and no significant improvement in overall survival. Although angiogenesis appears to have an important role in prostate cancer, the results of anti-angiogenic therapy in castration-resistant refractory disease have hitherto been disappointing. There are various possible explanations for this lack of efficacy in castration-resistant refractory disease: redundancy of angiogenic pathways, molecular heterogeneity of the disease, loss of tumor suppressor protein phosphatase and tensin homolog (PTEN) expression as well as various VEGF-A splicing isoforms with pro- and anti-angiogenic activity. A better understanding of the molecular mechanisms of angiogenesis may help to develop effective anti-angiogenic therapy in prostate cancer.
前列腺癌是西方世界男性最常见的癌症。尽管局部疾病可以通过既定的手术和放射药物治疗方法有效治疗，但去势抵抗性晚期前列腺癌的预后仍然令人失望。本研究的目的是综述血管生成在前列腺癌中的作用，并研究抗血管生成治疗的疗效。通过 Pubmed 对临床试验进行了抗血管生成治疗在前列腺癌中的疗效的文献检索。血管生成活性的替代标志物（微血管密度和血管内皮生长因子 A（VEGF-A）表达）与肿瘤分级、转移和预后相关。本综述纳入了 6 项随机研究：2 项局部和激素敏感疾病的 II 期试验（=60 和 99 例患者）和 4 项去势抵抗性难治性疾病的 III 期试验（=873 至 1224 例患者）。尽管 II 期试验显示无病生存期延长和疾病稳定，但 III 期试验发现毒性增加，总生存期无显著改善。尽管血管生成似乎在前列腺癌中具有重要作用，但迄今为止，抗血管生成治疗在去势抵抗性难治性疾病中的疗效令人失望。这种缺乏疗效在去势抵抗性难治性疾病中有多种可能的解释：血管生成途径的冗余、疾病的分子异质性、肿瘤抑制蛋白磷酸酶和张力蛋白同系物（PTEN）表达的丧失以及具有促血管生成和抗血管生成活性的各种 VEGF-A 剪接异构体。对血管生成分子机制的更好理解可能有助于开发前列腺癌的有效抗血管生成治疗。
