Advances in the development of therapeutic nucleic acids against cervical cancer.
Cervical cancer is the second most common neoplastic disease affecting women worldwide. Basic, clinical and epidemiological analyses indicate that expression of high-risk human papillomaviruses (HPVs) E6/E7 genes is the primary cause of cervical cancer and represent ideal targets for the application of therapeutic nucleic acids (TNAs). Antisense oligodeoxyribonucleotides (AS-ODNs) and ribozymes (RZs) are the most effective TNAs able to inhibit in vivo tumour growth by eliminating HPV-16 and HPV-18 E6/E7 transcripts. Expression of multiple RZs directed against alternative target sites by triplex expression systems may result in the abrogation of highly variable HPVs. More recently, RNA interference (RNAi) gene knockdown phenomenon, induced by small interfering RNA (siRNA), has demonstrated its potential value as an effective TNA for cervical cancer. siRNA and aptamers as TNAs will have a place in the armament for cervical cancer. TNAs against cervical cancer is in a dynamic state, and clinical trials will define the TNAs in preventive and therapeutic roles to control tumour growth, debulk tumour mass, prevent metastasis and facilitate immune interaction.
DiPaolo
Joseph A
JA
Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20894, USA. jd81a@nih.gov
Alvarez-Salas
Luis M
LM
D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D015967:Gene Expression Regulation, Viral; D018390:Gene Targeting; D015316:Genetic Therapy; D006801:Humans; D009690:Nucleic Acid Conformation; D009696:Nucleic Acids / Q000008:administration & dosage / Q000235:genetics / Q000627:therapeutic use*; D020319:Oligodeoxyribonucleotides, Antisense / Q000008:administration & dosage / Q000235:genetics / Q000627:therapeutic use; D009856:Oncogene Proteins, Viral / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology; D027383:Papillomaviridae / Q000235:genetics / Q000472:pathogenicity; D030361:Papillomavirus Infections / Q000235:genetics / Q000628:therapy; D034622:RNA Interference; D016337:RNA, Catalytic / Q000008:administration & dosage / Q000235:genetics / Q000627:therapeutic use; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics / Q000627:therapeutic use; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000628:therapy* / Q000821:virology
D009696:Nucleic Acids; D020319:Oligodeoxyribonucleotides, Antisense; D009856:Oncogene Proteins, Viral; D016337:RNA, Catalytic; D034741:RNA, Small Interfering