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Typical categorizations of chemotherapy agents do not include ribonucleases, a class of chemicals used widely in biochemistry research but rarely therapeutically. The ribonucleases are catalysts that break down RNA. Living cells employ ribonucleases in their metabolism. The rationale behind them as drugs is that they will destroy the
Scientists believe that ranpirnase binds to the extracellular membranes of the malignant cells at their anionic outposts. The drug makes its way through the membrane and degrades transfer RNA inside the cell. Transfer RNA is normally protected from natural enzymes by ribonuclease inhibitors, but the cell has no defenses against the foreign ribonuclease and. resulting in inhibition of protein synthesis and arresting of mitosis and condequent apoptosis. Clinical use of rapirnase will almost probably take place in a combination chemotherapy regimen with the antiobiotic doxorubicin.
There is also some scientific evidence that ranpirnase may be useful as an enhancer to radiation therapy. There was talk of trying the drugs on breast cancer and oesophageal cancer in phase II clinical trials. One good thing about ranpirnase is that in trials it did not induce such nasty common chemotherapy side effects as myelosuppression, mucositis, alopecia, cardiotoxicity, and hepatotoxicity. Alfacell’s U.S. patent on how to make ribonucleases (number 6 423 515 B1) lasts until 2020.
An amphibian oocyte ribonuclease (RNase) of 105 amino acids in length, ranpirnase was administered in clinical development as a single agent in patients with malignant mesothelioma (MM), at 480 microg/m2 intravenously weekly, analysis of survival indicated prolonged periods of stable disease in Phase II trials and a potential survival benefit, compared with doxorubicin. Results from the protocol-specified first interim analysis based on one-third of the required events have been reported and the company has the option to conduct a second interim analysis of the data at any point after 210 events. The efficacy of ranpirnase was compared with that of doxorubicin (head-to-head).
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