L-Nucleoside analogues against cancer-causing viruses have potential in the prevention, delayed onset and treatment of viral associated cancers.
It has been established that several types of cancers have a strong association with viruses. Thus, a potent antiviral compound without toxicity upon long-term usage will be useful not only for the treatment of viral diseases but also for the prevention or the delayed onset of those cancers that have a strong association with viruses. These compounds, depending upon their mechanism of action, could also potentially be useful for the treatment of those viral-associated cancers. L(-)Deoxynucleoside analogues were discovered in my laboratory and by others as an important class of antiviral and anti-cancer chemical entities. L(-)SddC (3TC, lamivudine), L(-)FTC, L(-)Fd4C, and L(-)FMAU are compounds with potent activity against hepatitis B virus (HBV), but with different biological and pharmacological profiles. These compounds may be useful in the prevention or delayed onset of hepatocellular carcinoma associated with HBV. L(-)I-OddU is a potent anti-Epstein-Barr virus (EBV) compound without cytotoxicity and animal toxicity upon long-term dosing, which allows drug concentration in plasma that are much higher than those that are antivirally active. This compound may have the potential to prevent B-cell lymphoma associated with patients undergoing organ transplants in addition to its potential use for the treatment of EBV infection. Furthermore, it may also be useful for the treatment of EBV-associated cancers. In this manuscript, the metabolism, mechanism of action and the resistance, as well as the potential use of this class of compounds targetted against HBV, will be discussed.
Cheng
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Yale University School of Medicine, New Haven, Conn, USA. susan.granata@yale.edu
D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000998:Antiviral Agents / Q000494:pharmacology*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000517:prevention & control* / Q000821:virology; D009705:Nucleosides / Q000494:pharmacology*; D009858:Oncogenic Viruses / Q000187:drug effects*
D000970:Antineoplastic Agents; D000998:Antiviral Agents; D009705:Nucleosides