Fay André P, Albiges Laurence, Bellmunt Joaquim
Dana-Farber Cancer Institute, Harvard Medical School 450 Brookline Avenue (DANA 1230), Boston, MA 02215, USA.
Expert Rev Anticancer Ther. 2015 Feb;15(2):151-6. doi: 10.1586/14737140.2015.1003047. Epub 2015 Jan 14.
Over 80% of men with castration-resistant prostate cancer have bone metastases. This condition can dramatically impact quality of life and is associated with short-term survival. Consequently, the development of bone-targeted therapies is a relevant topic on prostate cancer management. Hepatocyte growth factor receptor and vascular endothelial growth factor signaling pathways have been identified to play a role in prostate cancer progression and bone metastasis and are potential targets for therapeutic intervention. Early-phase studies have shown encouraging responses in bone metastases and pain control with cabozantinib, a multi-tyrosine kinase inhibitor targeting hepatocyte growth factor receptor and vascular endothelial growth factor receptor. Despite striking responses seen in some patients, preliminary results from a pivotal Phase III study have failed to produce survival benefit. This review encompasses preclinical and clinical data of cabozantinib in metastatic castration-resistant prostate cancer highlighting future research options for this agent.
超过80%的去势抵抗性前列腺癌男性患者发生骨转移。这种情况会显著影响生活质量，并与短期生存相关。因此，开发骨靶向治疗是前列腺癌管理中的一个相关话题。已确定肝细胞生长因子受体和血管内皮生长因子信号通路在前列腺癌进展和骨转移中起作用，并且是治疗干预的潜在靶点。早期研究显示，卡博替尼（一种靶向肝细胞生长因子受体和血管内皮生长因子受体的多酪氨酸激酶抑制剂）在骨转移和疼痛控制方面有令人鼓舞的反应。尽管在一些患者中观察到显著反应，但一项关键的III期研究的初步结果未能产生生存获益。本综述涵盖了卡博替尼在转移性去势抵抗性前列腺癌中的临床前和临床数据，突出了该药物未来的研究方向。
