University of Glasgow, Glasgow Western Infirmary, Division of Cancer Sciences and Molecular Pathology, Faculty of Medicine, Glasgow, UK.
Expert Opin Investig Drugs. 2010 May;19(5):605-14. doi: 10.1517/13543781003789388.
Once prostate cancer becomes castration-resistant, bone metastases are a significant problem and treatment options are limited. As a result, there is a need for more effective therapies that have antitumor and anti-bone metastatic effects. Because Src and Src-family kinases (SFKs) are involved in multiple signaling pathways central to prostate cancer development, progression, and metastasis, in addition to normal and pathologic osteoclast activities, Src inhibition represents a valid therapeutic strategy for investigation.
Here, current treatment options for advanced prostate cancer, the preclinical rationale behind using Src inhibitors, emerging data from clinical trials of Src inhibitors in prostate cancer, and future therapeutic directions are described. Data published in peer-reviewed journals within the last 20 years or presented at recent European or American Society of Clinical Oncology conferences have been reviewed.
Readers will gain an insight into the development of therapeutic Src inhibitors, including dasatinib and saracatinib; an understanding of their effects on prostate cancer cells and the bone microenvironment; and emerging clinical data.
Src is implicated in prostate cancer progression and metastasis, therefore treatment with Src inhibitors warrants further investigation.
一旦前列腺癌对去势产生抗药性,骨转移就是一个严重的问题,治疗选择有限。因此,需要更有效的治疗方法,具有抗肿瘤和抗骨转移作用。由于Src 和 Src 家族激酶(SFKs)参与前列腺癌发展、进展和转移的多个信号通路,以及正常和病理破骨细胞的活性,Src 抑制代表了一个有价值的治疗策略。
目前晚期前列腺癌的治疗选择,使用 Src 抑制剂的临床前依据,在前列腺癌中进行的 Src 抑制剂临床试验的新数据,以及未来的治疗方向。对过去 20 年在同行评审期刊上发表的或在最近的欧洲或美国临床肿瘤学会会议上提交的资料进行了综述。
读者将深入了解治疗性 Src 抑制剂的开发,包括达沙替尼和沙卡替尼;了解它们对前列腺癌细胞和骨微环境的影响;以及新兴的临床数据。
Src 参与了前列腺癌的进展和转移,因此治疗用 Src 抑制剂值得进一步研究。