Ranpirnase (Onconase^®), a cytotoxic amphibian ribonuclease, manipulates tumour physiological parameters as a selective killer and a potential enhancer for chemotherapy and radiation in cancer therapy

Abstract

Background: Ranpirnase, a cytotoxic amphibian ribonuclease, is effective against cancer cells, inducing apoptosis independently of p53 protein. Onconase^® (the smallest member of the RNase A superfamily) has moved into clinical testing in the US and Europe. Objective: The main focuses of this review are to examine the manipulation of tumour physiological parameters by ranpirnase and discuss its molecular, pharmacological and physiological roles in preclinical and clinical trials in terms of benefits and toxicity. Methods: Relevant literature, including the author's unpublished presentations at recent conferences, was examined. Results/conclusion: In animal studies, improvements in tumour physiology (i.e., increased blood flow, inhibited oxygen consumption, increased oxygenation and decreased tumour hypertension) and selectively enhanced radiation responses (i.e., increased radiation sensitivity and inhibited repair of sublethal and potentially lethal damage) were observed after ranpirnase treatment in preclinical tumour models. Ranpirnase is a promising candidate as an enhancer for radiation- and chemotherapy. Ongoing clinical trials promise to further improve the treatment of mesothelioma and lung cancer.

Keywords::

• cancer therapy
• chemotherapy
• cytotoxic amphibian ribonuclease
• radiation
• ranpirnase