title: Ranpirnase and its potential for the treatment of unresectable malignant mesothelioma.
abstract: Ribonucleases are a superfamily of enzymes which operate at the crossroads of transcription and translation, catalyzing the degradation of RNA; they can be cytotoxic because the cleavage of RNA renders indecipherable its information. Ranpirnase is a novel ribonuclease which preferentially degrades tRNA, thus leading to inhibition of protein synthesis and, ultimately, to cytostasis and cytotoxicity. Ranpirnase has demonstrated antitumor activity both in vitro and in vivo in several tumor models. The maximum tolerated dose emerging from phase I studies was 960 g/m(2), with renal toxicity as the main dose-limiting toxicity. A large phase II trial showed that ranpirnase has disease-modifying activity against malignant mesothelioma. Ranpirnase proved to be superior to doxorubicin in a phase III trial, while preliminary results of another large, phase III trial, suggest that the combination of ranpirnase and doxorubicin could be more effective than doxorubicin alone. In all the above studies, ranpirnase seems to act mainly as a cytostatic rather than a cytotoxic drug, stabilizing progressive disease and potentially prolonging patients' survival. Ranpirnase may thus find its niche in combination with doxorubicin for mesothelioma as a second-line therapy, where no standard of care presently exists.
authors.affiliation: Medical Oncology and Laboratory of Pre-Clinical Oncology and Developmental Therapeutics, I.R.C.C.S. San Matteo University Hospital Foundation, Pavia, Italy.
authors.forename: Camillo
authors.initials: C
authors.lastname: Porta
authors.forename: Chiara
authors.initials: C
authors.lastname: Paglino
authors.forename: Luciano
authors.initials: L
authors.lastname: Mutti
references.citation: J Mol Biol. 1996 Apr 19;257(5):992-1007
references.pmid: 8632481
references.citation: Mol Cancer Ther. 2005 May;4(5):835-42
references.pmid: 15897248
references.citation: Cancer Chemother Pharmacol. 2008 Jul;62(2):337-46
references.pmid: 18064463
references.citation: J Natl Cancer Inst. 1990 Jan 17;82(2):151-3
references.pmid: 2294226
references.citation: Blood. 2000 Jul 1;96(1):307-13
references.pmid: 10891466
references.citation: Cell Tissue Kinet. 1988 May;21(3):169-82
references.pmid: 3224365
references.citation: Anticancer Res. 2007 Jan-Feb;27(1A):299-307
references.pmid: 17352247
references.citation: Chem Biol. 2001 May;8(5):405-13
references.pmid: 11358688
references.citation: Cell Mol Life Sci. 1998 Aug;54(8):775-84
references.pmid: 9760986
references.citation: Br J Cancer. 1999 Feb;79(3-4):666-72
references.pmid: 10027347
references.citation: Biotechnol Lett. 2006 Oct;28(20):1615-22
references.pmid: 16902846
references.citation: J Clin Oncol. 2001 Jan 1;19(1):265-72
references.pmid: 11134222
references.citation: Invest New Drugs. 2001;19(3):255-60
references.pmid: 11561684
references.citation: Expert Opin Biol Ther. 2006 Apr;6(4):391-9
references.pmid: 16548765
references.citation: Int J Oncol. 1995 Apr;6(4):889-97
references.pmid: 21556617
references.citation: Cancer Invest. 2005;23(7):643-50
references.pmid: 16305992
references.citation: Chest. 1998 Mar;113(3):723-31
references.pmid: 9515850
references.citation: Cancer Chemother Pharmacol. 1999;44(2):164-9
references.pmid: 10412952
references.citation: Nat Clin Pract Oncol. 2008 Mar;5(3):136-47
references.pmid: 18227828
references.citation: Int J Oncol. 2007 Sep;31(3):663-9
references.pmid: 17671695
references.citation: Mol Biosyst. 2005 Oct;1(4):294-302
references.pmid: 16880994
references.citation: J Clin Oncol. 2002 Jan 1;20(1):274-81
references.pmid: 11773179
references.citation: Anticancer Res. 2000 Mar-Apr;20(2A):1037-40
references.pmid: 10810394
references.citation: Proteins. 1992 Nov;14(3):392-400
references.pmid: 1438177
references.citation: J Biol Chem. 1991 Jan 5;266(1):245-51
references.pmid: 1985896
references.citation: Adv Exp Med Biol. 2007;599:53-9
references.pmid: 17727247
references.citation: BioDrugs. 2008;22(1):53-8
references.pmid: 18215091
references.citation: Adv Exp Med Biol. 2003;530:187-96
references.pmid: 14562716
references.citation: J Biol Chem. 1993 May 15;268(14):10686-93
references.pmid: 8486718
references.citation: Proc Natl Acad Sci U S A. 1998 Sep 1;95(18):10407-12
references.pmid: 9724716
references.citation: Leukemia. 1998 Aug;12(8):1241-8
references.pmid: 9697879
references.citation: J Natl Cancer Inst. 1996 Jun 5;88(11):747-53
references.pmid: 8637029
references.citation: Int J Oncol. 1992 Dec;1(7):779-85
references.pmid: 21584616
references.citation: J Surg Oncol. 2000 Mar;73(3):164-71
references.pmid: 10738271
references.citation: Cancer Res. 1996 Sep 15;56(18):4180-6
references.pmid: 8797589
references.citation: Semin Oncol. 2005 Jun;32(3):336-50
references.pmid: 15988688
references.citation: Nat Rev Cancer. 2007 Feb;7(2):147-54
references.pmid: 17251920
references.citation: Int J Oncol. 1998 Jul;13(1):11-6
references.pmid: 9625797
references.citation: Cancer Lett. 2007 May 18;250(1):107-16
references.pmid: 17084521
references.citation: Nature. 1955 Jul 2;176(4470):36-7
references.pmid: 14394135
references.citation: Cancer Res. 2000 Apr 1;60(7):1983-94
references.pmid: 10766189
references.citation: Int J Oncol. 1993 Jul;3(1):57-64
references.pmid: 21573326
references.citation: Cell Tissue Kinet. 1990 May;23(3):237-46
references.pmid: 2357721
references.citation: In Vivo. 2007 Sep-Oct;21(5):721-8
references.pmid: 18019404
references.citation: Experientia. 1954 Dec 15;10(12):500-1
references.pmid: 14353090
references.citation: Curr Pharm Biotechnol. 2007 Dec;8(6):318-9
references.pmid: 18289038
references.citation: Blood. 2001 Jan 15;97(2):528-35
references.pmid: 11154233
references.citation: Mol Cell Biol Res Commun. 2000 Aug;4(2):122-8
references.pmid: 11170843