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.
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Relevant literature, including the author's unpublished presentations at recent conferences, was examined.


CONCLUSIONS
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.
Lee
Intae
I
University of Pennsylvania, Department of Radiology, B6 Blockley Hall, 423 Guardian Drive, Philadelphia, PA 19104-6069, USA. intaelee@gmail.com
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use* / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects; D002986:Clinical Trials as Topic / Q000706:statistics & numerical data; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D045604:Extracellular Fluid / Q000187:drug effects; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D016513:Mice, SCID; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors; D009369:Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000532:radiotherapy*; D010101:Oxygen Consumption / Q000187:drug effects; D000081082:Phosphoinositide-3 Kinase Inhibitors; D020871:RNA Stability / Q000187:drug effects; D012334:RNA, Neoplasm / Q000378:metabolism; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology / Q000627:therapeutic use* / Q000633:toxicity; D011894:Rana pipiens; D012260:Ribonucleases / Q000494:pharmacology / Q000627:therapeutic use* / Q000633:toxicity; D015398:Signal Transduction / Q000187:drug effects
D000970:Antineoplastic Agents; D009363:Neoplasm Proteins; D000081082:Phosphoinositide-3 Kinase Inhibitors; D012334:RNA, Neoplasm; D011838:Radiation-Sensitizing Agents; D012260:Ribonucleases; C058703:ranpirnase