宫颈癌：超越分子发病机制的靶向治疗进展
Cervical Cancer: Development of Targeted Therapies Beyond Molecular Pathogenesis.
作者信息
Knoff Jayne, Yang Benjamin, Hung Chien-Fu, Wu T-C
机构信息
Department of Pathology, Johns Hopkins University, Baltimore, MD 21205, USA.
Department of Pathology, Johns Hopkins University, Baltimore, MD 21205, USA ; Department of Oncology, Johns Hopkins University, Baltimore, MD 21205, USA.
出版信息
Curr Obstet Gynecol Rep. 2014 Mar 1;3(1):18-32. doi: 10.1007/s13669-013-0068-1.
It is well known that human papillomavirus (HPV) is the causative agent of cervical cancer. The integration of HPV genes into the host genome causes the upregulation of E6 and E7 oncogenes. E6 and E7 proteins inactivate and degrade tumor suppressors p53 and retinoblastoma, respectively, leading to malignant progression. HPV E6 and E7 antigens are ideal targets for the development of therapies for cervical cancer and precursor lesions because they are constitutively expressed in infected cells and malignant tumors but not in normal cells and they are essential for cell immortalization and transformation. Immunotherapies are being developed to target E6/E7 by eliciting antigen-specific immune responses. siRNA technologies target E6/E7 by modulating the expression of the oncoproteins. Proteasome inhibitors and histone deacetylase inhibitors are being developed to indirectly target E6/E7 by interfering with their oncogenic activities. The ultimate goal for HPV-targeted therapies is the progression through clinical trials to commercialization.
众所周知，人乳头瘤病毒（HPV）是宫颈癌的致病因子。HPV基因整合到宿主基因组中会导致致癌基因E6和E7的上调。E6和E7蛋白分别使肿瘤抑制因子p53和视网膜母细胞瘤失活并降解，从而导致恶性进展。HPV E6和E7抗原是开发宫颈癌及癌前病变治疗方法的理想靶点，因为它们在受感染细胞和恶性肿瘤中持续表达，但在正常细胞中不表达，并且它们对于细胞永生化和转化至关重要。正在开发免疫疗法，通过引发抗原特异性免疫反应来靶向E6/E7。siRNA技术通过调节癌蛋白的表达来靶向E6/E7。正在开发蛋白酶体抑制剂和组蛋白脱乙酰酶抑制剂，通过干扰其致癌活性来间接靶向E6/E7。针对HPV的治疗方法的最终目标是通过临床试验推进到商业化阶段。
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