del Campo Josep Maria, Prat Aleix, Gil-Moreno Antonio, Pérez José, Parera Marta
Department of Medical Oncology, Vall d'Hebron University Hospital, Barcelona, Spain.
Gynecol Oncol. 2008 Sep;110(3 Suppl 2):S72-6. doi: 10.1016/j.ygyno.2008.04.016. Epub 2008 Jun 9.
Effective cytotoxic treatment options for advanced cervical cancer are exceedingly limited. Cisplatin-based combination chemotherapy, the most commonly used cytotoxic therapy, has produced response rates ranging from 20% to 30% and overall survival of less than 10 months. Because of the minimal degree of success with cytotoxic therapies and the poor prognosis of patients with this disease, interest has increased in targeted therapeutics for the treatment of cervical cancer. In recent years, significant improvements in our understanding of the altered molecular events in tumor cells have led to the discovery of new targets and agents for clinical testing. Two of these promising targets are epidermal growth factor receptor (EGFR) and the vascular endothelial growth factor (VEGF) signaling pathway, which play critical roles in tumor growth and angiogenesis. Two monoclonal antibodies, cetuximab, which targets EGFR, and bevacizumab, which target the VEGF signaling pathway, are being evaluated as monotherapy and in combination with other agents and/or radiotherapy for the treatment of cervical cancer. In addition, VEGF receptor tyrosine kinase inhibitors, such as sorafenib and pazopanib, are being studied in phase I/II clinical trials. In this review, we discuss potential molecular targets and novel therapeutic strategies that are being investigated for the treatment of cervical cancer.
对于晚期宫颈癌,有效的细胞毒性治疗方案极为有限。以顺铂为基础的联合化疗是最常用的细胞毒性疗法,其缓解率在20%至30%之间,总生存期不足10个月。由于细胞毒性疗法取得的成功极小,且该疾病患者预后较差,因此针对宫颈癌治疗的靶向疗法的关注度有所增加。近年来,我们对肿瘤细胞中分子事件改变的理解有了显著进步,从而发现了用于临床试验的新靶点和药物。其中两个有前景的靶点是表皮生长因子受体(EGFR)和血管内皮生长因子(VEGF)信号通路,它们在肿瘤生长和血管生成中起关键作用。两种单克隆抗体,即靶向EGFR的西妥昔单抗和靶向VEGF信号通路的贝伐单抗,正在作为单一疗法以及与其他药物和/或放疗联合用于治疗宫颈癌进行评估。此外,VEGF受体酪氨酸激酶抑制剂,如索拉非尼和帕唑帕尼,正在进行I/II期临床试验研究。在本综述中,我们讨论了正在研究的用于治疗宫颈癌的潜在分子靶点和新型治疗策略。