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Insights into the broad cellular effects of nelfinavir and the HIV protease inhibitors supporting their role in cancer treatment and prevention.

AbstractPURPOSE OF REVIEW:
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.
RECENT FINDINGS:
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.
SUMMARY:
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.
AuthorsSoren Gantt, Corey Casper, Richard F Ambinder
JournalCurrent opinion in oncology (Curr Opin Oncol) Vol. 25 Issue 5 Pg. 495-502 (Sep 2013) ISSN: 1531-703X [Electronic] United States
PMID23872785 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Review)
Chemical References
  • Angiogenesis Inhibitors
  • HIV Protease Inhibitors
  • Proto-Oncogene Proteins c-akt
  • Nelfinavir
Topics
  • Angiogenesis Inhibitors (therapeutic use)
  • Clinical Trials as Topic
  • HIV Protease Inhibitors (therapeutic use)
  • Humans
  • Nelfinavir (therapeutic use)
  • Neoplasms (drug therapy, prevention & control)
  • Proto-Oncogene Proteins c-akt (antagonists & inhibitors)

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