title: HIV-protease inhibitors for the treatment of cancer: Repositioning HIV protease inhibitors while developing more potent NO-hybridized derivatives?
abstract: The possible use of HIV protease inhibitors (HIV-PI) as new therapeutic option for the treatment of cancer primarily originated from their success in treating HIV-related Kaposi's sarcoma (KS). While these findings were initially attributed to immune reconstitution and better control of oncogenic viral infections, the number of reports on solid tumors, KS, lymphoma, fibrosarcoma, multiple myeloma and prostate cancer suggest other mechanisms for the anti-neoplastic activity of PIs. However, a major drawback for the possible adoption of HIV-PIs in the therapy of cancer relies on their relatively weak anticancer potency and important side effects. This has propelled several groups to generate derivatives of HIV-PIs for anticancer use, through modifications such as attachment of different moieties, ligands and transporters, including saquinavir-loaded folic acid conjugated nanoparticles and nitric oxide (NO) derivatives of HIV-PIs. In this article, we discuss the current preclinical and clinical evidences for the potential use of HIV-PIs, and of novel derivatives, such as saquinavir-NO in the treatment of cancer.
authors.affiliation: Department of Immunology, Institute for Biological Research "Sinisa Stankovic," Belgrade University, Serbia.
authors.forename: Danijela
authors.initials: D
authors.lastname: Maksimovic-Ivanic
authors.affiliation: Department of Biomedical and Biotechnological Sciences, University of Catania, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Fagone
authors.affiliation: Department of Microbiology and Immunology, Brody School of Medicine at East Carolina University, Greenville, NC.
authors.forename: James
authors.initials: J
authors.lastname: McCubrey
authors.affiliation: Institute for Inflammation Research (IIR), Rigshospitalet University Hospital, Copenhagen, Denmark.
authors.forename: Klaus
authors.initials: K
authors.lastname: Bendtzen
authors.affiliation: Department of Immunology, Institute for Biological Research "Sinisa Stankovic," Belgrade University, Serbia.
authors.forename: Sanja
authors.initials: S
authors.lastname: Mijatovic
authors.affiliation: Department of Biomedical and Biotechnological Sciences, University of Catania, Italy.
authors.forename: Ferdinando
authors.initials: F
authors.lastname: Nicoletti
mesh_terms: D023241:Antiretroviral Therapy, Highly Active; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy* / Q000821:virology; D017320:HIV Protease Inhibitors / Q000627:therapeutic use*; D015497:HIV-1 / Q000187:drug effects / Q000472:pathogenicity; D006801:Humans; D009369:Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000821:virology; D009569:Nitric Oxide / Q000378:metabolism; D019258:Saquinavir / Q000031:analogs & derivatives / Q000627:therapeutic use; D012514:Sarcoma, Kaposi / Q000150:complications / Q000188:drug therapy* / Q000821:virology
chemical_list: D017320:HIV Protease Inhibitors; C557004:saquinavir-NO; D009569:Nitric Oxide; D019258:Saquinavir
keywords: HIV protease inhibitors; cancer therapeutics; saquinavir-NO