Ribonucleases as a novel pro-apoptotic anticancer strategy: Review of the preclinical and clinical data for ranpirnase

John Costanzi, David Sidransky, Ami Navon, Howard Goldsweig

Research output: Contribution to journalReview articlepeer-review

Abstract

Cytotoxic ribonucleases (RNases), such as ranpiranase, represent a novel mechanism-based approach to anticancer therapy. These relatively small proteins selectively attack malignant cells, triggering apoptotic response and inhibiting protein synthesis. Ranpirnase, originally isolated from oocytes of Rana pipiens, is a member of a family of endoribonucleases. The anticancer effects of ranpiranase have been documented in both in vitro and in vivo experimental tumor models. The effects of ranpiranase appear to be selective for cancer cells. Based on Phase I study data, the maximum tolerated dose (MTD) was 960 μg/m2, with the dose-limiting toxicity (DLT) characterized by proteinuria with or without azotemia, peripheral edema, and fatigue. Ranpirnase did not induce myelosuppression, mucositis, alopecia, cardiotoxicity, coagulopathy, hepatotoxicity, or adverse metabolic effects. Phase II tumor-specific trials investigated the activity of ranpirnase in malignant mesothelioma, breast cancer, non-small cell lung cancer, and renal cell cancer. A Phase III randomized study in malignant mesothelioma patients compares the combination of ranpirnase plus doxorubicin to doxorubicin monotherapy.

Original languageEnglish (US)
Pages (from-to)643-650
Number of pages8
JournalCancer Investigation
Volume23
Issue number7
DOIs
StatePublished - 2005

Keywords

  • Anticancer therapy
  • Ranpiranase
  • Ribonucleases

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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