Future of RNAi-based therapies for human papillomavirus-associated cervical cancer

Abstract

Over 99% of cervical cancers are associated with infection of high-risk type human papillomaviruses (HPV). These viruses infect epithelial cells lining the cervix and express the early viral genes E6 and E7, which are oncogenes and are primarily responsible for the transformation of the epithelial cells. The continuous expression of those genes is essential for maintenance of the cancer cell phenotype and viability. These viral genes can be silenced using oligonucleotide-based techniques, for example RNAi, antisense RNA and ribozymes. In spite of promising results in vitro and in vivo, in mice, these methods have thus far proved unsuccessful in humans, owing to the lack of an effective delivery system amongst other limitations. In this review we will discuss potential gene-silencing strategies in cervical cancer that would target both viral genes such as E6 and E7, and cellular genes that become deregulated such as E2F, p53, Akt, mTor, NF-?B or Bcl-2. By investigating these approaches we may generate an effective treatment for HPV-induced cervical cancer using gene silencing.