title: Cervical Cancer: Development of Targeted Therapies Beyond Molecular Pathogenesis.
abstract: 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.
authors.affiliation: Department of Pathology, Johns Hopkins University, Baltimore, MD 21205, USA.
authors.forename: Jayne
authors.initials: J
authors.lastname: Knoff
authors.affiliation: Department of Pathology, Johns Hopkins University, Baltimore, MD 21205, USA.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Yang
authors.affiliation: Department of Pathology, Johns Hopkins University, Baltimore, MD 21205, USA ; Department of Oncology, Johns Hopkins University, Baltimore, MD 21205, USA.
authors.forename: Chien-Fu
authors.initials: CF
authors.lastname: Hung
authors.affiliation: Department of Pathology, Johns Hopkins University, Baltimore, MD 21205, USA ; Department of Obstetrics and Gynecology, Johns Hopkins University, Baltimore, MD 21205, USA ; Department of Molecular Microbiology and Immunology, Johns Hopkins University, Baltimore, MD 21205, USA ; Department of Oncology, Johns Hopkins University, Baltimore, MD 21205, USA.
authors.forename: T-C
authors.initials: TC
authors.lastname: Wu
keywords: HPV-targeted therapies; cervical cancer; gynecological cancer; histone deacetylase inhibitor; human papillomavirus; proteasome inhibitor; siRNA; targeted therapy; vaccine