Ranpirnase and its potential for the treatment of unresectable malignant mesothelioma

Research output: Contribution to journalArticle

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/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' 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.

Original languageEnglish
Pages (from-to)601-609
Number of pages9
JournalBiologics: Targets and Therapy
Volume2
Issue number4
Publication statusPublished - 2008

Fingerprint

Doxorubicin
Ribonucleases
Therapeutics
RNA Cleavage
Maximum Tolerated Dose
Mesothelioma
RNA Stability
Cytostatic Agents
Standard of Care
Transfer RNA
ranpirnase
Malignant Mesothelioma
Kidney
Survival
Enzymes
Pharmaceutical Preparations
Neoplasms
Proteins

Keywords

  • Antitumor activity
  • Doxorubicin
  • Mesothelioma
  • Ranpirnase
  • Ribonucleases

ASJC Scopus subject areas

  • Oncology
  • Immunology and Allergy
  • Pharmacology (medical)
  • Gastroenterology
  • Rheumatology

Cite this

Ranpirnase and its potential for the treatment of unresectable malignant mesothelioma. / Porta, Camillo; Paglino, Chiara; Mutti, Luciano.

In: Biologics: Targets and Therapy, Vol. 2, No. 4, 2008, p. 601-609.

Research output: Contribution to journalArticle

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