Antitumor potential of acyclic nucleoside phosphonates.
Acyclic nucleoside phosphonates such as HPMPC (cidofovir) and PMEA (adefovir) have been identified as broad-spectrum antiviral agents that are effective against herpes-, retro- and hepadnavirus infections (PMEA) and herpes-, pox-, adeno-, polyoma-, and papillomavirus infections (HPMPC). Here we show that HPMPC and PMEA also offer great potential as antitumor agents, through the induction of tumor cell differentiation (PMEA), inhibition of angiogenesis (HPMPC) and induction of apoptosis (HPMPC). In vivo tumor regressions have been noted for choriocarcinoma (PMEA) in rats, hemangioma (HPMPC) in rats and papillomatous lesions (HPMPC) in humans. Acyclic nucleoside phosphonates can be considered as a new dimension to the discipline of chemotherapy. They have a unique mode of action that is targeted at (viral or tumoral) DNA synthesis. They exhibit a pronounced and prolonged anti-viral and/or tumoral activity that can persist for days or weeks after a single administration. Most importantly, they have a uniquely broad spectrum of indications for clinical use, encompassing both DNA- and retrovirus infections, as well as various forms of cancer of both viral and non-viral origin.
De Clercq
E
E
Rega Institute for Medical Research, K.U. Leuven, Belgium.
Andrei
G
G
Balzarini
J
J
Hatse
S
S
Liekens
S
S
Naesens
L
L
Neyts
J
J
Snoeck
R
R
D000225:Adenine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002822:Choriocarcinoma / Q000473:pathology; D000077404:Cidofovir; D003596:Cytosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D009369:Neoplasms / Q000473:pathology / Q000821:virology; D009389:Neovascularization, Pathologic / Q000517:prevention & control; D063065:Organophosphonates; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D027383:Papillomaviridae / Q000472:pathogenicity; D051381:Rats; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D063065:Organophosphonates; D009943:Organophosphorus Compounds; C053001:adefovir; D003596:Cytosine; D000225:Adenine; D000077404:Cidofovir