Antitumor potential of acyclic nucleoside phosphonates

Acyclic nucleoside phosphonates such as HPMPC (cidofovir) and PMEA (adefovi r) have been identified as broad-spectrum antiviral agents that are effecti ve 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, throug h the induction of tumor cell differentiation (PMEA), inhibition of angioge nesis (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 phosph onates can be considered as a new dimension to the discipline of chemothera py. 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 administ ration. Most importantly, they have a uniquely broad spectrum of indication s for clinical use, encompassing both DNA- and retrovirus infections, as we ll as various forms of cancer of both viral and non-viral origin.