Ranpirnase and its potential for the treatment of unresectable malignant mesothelioma

Camillo Porta1, Chiara Paglino1, Luciano Mutti21Medical Oncology and Laboratory of Pre-Clinical Oncology and Developmental Therapeutics, I.R.C.C.S. San Matteo University Hospital Foundation, Pavia, Italy; 2Local Health Authority 6, Piedmont, ItalyAbstract: Ribonucleases are a superfamily of enzymes...

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Autores principales:	Camillo Porta, Chiara Paglino, Luciano Mutti
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2008
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/6dbceac834b74d9c820efe3118c15925
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spelling	oai:doaj.org-article:6dbceac834b74d9c820efe3118c159252021-12-02T04:10:33ZRanpirnase and its potential for the treatment of unresectable malignant mesothelioma1177-54751177-5491https://doaj.org/article/6dbceac834b74d9c820efe3118c159252008-08-01T00:00:00Zhttp://www.dovepress.com/ranpirnase-and-its-potential-for-the-treatment-of-unresectable-maligna-a1947https://doaj.org/toc/1177-5475https://doaj.org/toc/1177-5491Camillo Porta1, Chiara Paglino1, Luciano Mutti21Medical Oncology and Laboratory of Pre-Clinical Oncology and Developmental Therapeutics, I.R.C.C.S. San Matteo University Hospital Foundation, Pavia, Italy; 2Local Health Authority 6, Piedmont, ItalyAbstract: 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/m2, 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&rsquo; 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.Keywords: ranpirnase, mesothelioma, ribonucleases, doxorubicin, antitumor activity Camillo PortaChiara PaglinoLuciano MuttiDove Medical PressarticleMedicine (General)R5-920ENBiologics: Targets & Therapy, Vol 2008, Iss Issue 4, Pp 601-609 (2008)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Camillo Porta Chiara Paglino Luciano Mutti Ranpirnase and its potential for the treatment of unresectable malignant mesothelioma
description	Camillo Porta1, Chiara Paglino1, Luciano Mutti21Medical Oncology and Laboratory of Pre-Clinical Oncology and Developmental Therapeutics, I.R.C.C.S. San Matteo University Hospital Foundation, Pavia, Italy; 2Local Health Authority 6, Piedmont, ItalyAbstract: 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/m2, 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&rsquo; 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.Keywords: ranpirnase, mesothelioma, ribonucleases, doxorubicin, antitumor activity
format	article
author	Camillo Porta Chiara Paglino Luciano Mutti
author_facet	Camillo Porta Chiara Paglino Luciano Mutti
author_sort	Camillo Porta
title	Ranpirnase and its potential for the treatment of unresectable malignant mesothelioma
title_short	Ranpirnase and its potential for the treatment of unresectable malignant mesothelioma
title_full	Ranpirnase and its potential for the treatment of unresectable malignant mesothelioma
title_fullStr	Ranpirnase and its potential for the treatment of unresectable malignant mesothelioma
title_full_unstemmed	Ranpirnase and its potential for the treatment of unresectable malignant mesothelioma
title_sort	ranpirnase and its potential for the treatment of unresectable malignant mesothelioma
publisher	Dove Medical Press
publishDate	2008
url	https://doaj.org/article/6dbceac834b74d9c820efe3118c15925
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Ranpirnase and its potential for the treatment of unresectable malignant mesothelioma

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