TY - JOUR
T1 - Insights into the broad cellular effects of nelfinavir and the HIV protease inhibitors supporting their role in cancer treatment and prevention
AU - Gantt, Soren
AU - Casper, Corey
AU - Ambinder, Richard F.
PY - 2013/9
Y1 - 2013/9
N2 - PURPOSE 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.
AB - PURPOSE 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.
KW - Cancer
KW - HIV protease inhibitor
KW - Kaposi sarcoma
KW - Nelfinavir
KW - Treatment
UR - http://www.scopus.com/inward/record.url?scp=84883225852&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84883225852&partnerID=8YFLogxK
U2 - 10.1097/CCO.0b013e328363dfee
DO - 10.1097/CCO.0b013e328363dfee
M3 - Review article
C2 - 23872785
AN - SCOPUS:84883225852
SN - 1040-8746
VL - 25
SP - 495
EP - 502
JO - Current opinion in oncology
JF - Current opinion in oncology
IS - 5
ER -