title: Insights into the broad cellular effects of nelfinavir and the HIV protease inhibitors supporting their role in cancer treatment and prevention.
abstract: OBJECTIVE
  The development of HIV protease inhibitors more than two decades ago heralded a new era in HIV care, changing the infection from universally fatal to chronic but controllable. With the widespread use of protease inhibitors, there was a reduction in the incidence and mortality of HIV-associated malignancies. Studies later found these drugs to have promising direct antitumor effects.
  
  
  RESULTS
  Protease inhibitors have a wide range of effects on several cellular pathways that are important for tumorigenesis and independent of inhibition of the HIV protease, including reducing angiogenesis and cell invasion, inhibition of the Akt pathway, induction of autophagy, and promotion of apoptosis. Among protease inhibitors, nelfinavir appears to have the most potent and broad antineoplastic activities, and also affects replication of the oncogenic herpesviruses Kaposi sarcoma-associated herpesvirus and Epstein-Barr virus. Nelfinavir is being studied for the prevention and treatment of a wide range of malignancies in persons with and without HIV infection.
  
  
  CONCLUSIONS
  Nelfinavir and other protease inhibitors are well tolerated, oral drugs that have promising antitumor properties, and may prove to play an important role in the prevention and treatment of several cancers. Additional insights into protease inhibitors' mechanisms of action may lead to the development of novel cancer chemotherapy agents.
authors.affiliation: University of British Columbia, Child & Family Research Institute, Room A5-147, 950 West 28th Avenue, Vancouver, BC V5Z 4H4, Canada. sgantt@cw.bc.ca
authors.forename: Soren
authors.initials: S
authors.lastname: Gantt
authors.forename: Corey
authors.initials: C
authors.lastname: Casper
authors.forename: Richard F
authors.initials: RF
authors.lastname: Ambinder
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D017320:HIV Protease Inhibitors / Q000627:therapeutic use*; D006801:Humans; D019888:Nelfinavir / Q000627:therapeutic use; D009369:Neoplasms / Q000188:drug therapy* / Q000517:prevention & control; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors
chemical_list: D020533:Angiogenesis Inhibitors; D017320:HIV Protease Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D019888:Nelfinavir