Abstract
One of perspective trends in the systemic anti-cancer treatment is the use of enzymes splitting ribonucleic acid - ribonucleases /RNases/. A number of both natural and genetically modified RNases are currently being subjected to different stages of studies and some of them are promising as efficient anticancer agents.
RNase from frog eggs and embryos - onconase (ranpirnase) - is currently used in the mesothelioma treatment and subjected to clinical trials in further indications (breast, kidney, and non-small cell lung cancer). The cytostatic effects result from proteosynthesis inhibition due to the tRNA splitting.
The splitting of rRNA, activation of caspases and reduction of the Bcl-2 expression also contribute to this action. The final result is the tumor cell apoptosis induction, as demonstrated in many in vivo as well as in vitro experiments.
RNases bound to antibodies (anti Erb-2 and anti CD 22) were successfully tested in preclinical experimental studies. Experiments demonstrating synergism of onconase with cytostatics and interferons offer promising results.
Side effects belonging to factors restricting the use of cytostatics are only mild with the use of RNases. Experience with onconase application in more than 850 patients demonstrated the main undesirable effects to be "flulike symptoms", vasodilatation, paresthesia, peripheral oedemas, allergic reactions and nephrotoxicity manifested by proteinuria and sometimes also by renal function impairments.
The results of experiments and clinical trials suggest that inclusion of onconase and/or other RNases into chemotherapeutic protocols could contribute to enhancement of the therapeutic effects without increase of the toxicity.