Abstract
Ranpirnase (ONCONASE®, a trademark of Alfacell Corporation), a cytotoxic amphibian ribonuclease, is known to be selectively tumoricidal against cancer cells. This article briefly summarizes in vitro and in vivo tumoricidal studies of ranpirnase. It proposes mechanisms of ranpirnase based on preclinical and clinical trials. Ranpirnase significantly inhibited oxygen consumption while demonstrating improvement in several tumor physiological parameters including tumor blood flow (TBF). Ranpirnase showed chemo-sensitization with various chemotherapeutic agents in vitro and in vivo. Ranpirnase significantly reduced the tumor hypertension, the major physiological barrier of therapeutic drug delivery to solid tumors. This resulted in increased tumor penetration and selectively increased TBF. This enhanced efficacy of chemotherapeutic agents including cisplatin and doxorubicin. The possible ranpirnase-related signal transduction pathways are discussed in the context of the enhanced induction of apoptosis and inhibition of protein synthesis. As a selective cancer killer ranpirnase may be a promising candidate for improving the treatment of mesothelioma and lung cancer patients.
Keywords: Ranpirnase, ONCONASE®, mesothelioma, lung cancer, apoptosis, protein inhibition, tumor hypertension, tumor blood flow
Current Cancer Therapy Reviews
Title: Physiological and Molecular Role of Ranpirnase on Cancer Treatment
Volume: 6 Issue: 1
Author(s): Intae Lee, Daehong Kim, Jihean Lee and Kuslima Shogen
Affiliation:
Keywords: Ranpirnase, ONCONASE®, mesothelioma, lung cancer, apoptosis, protein inhibition, tumor hypertension, tumor blood flow
Abstract: Ranpirnase (ONCONASE®, a trademark of Alfacell Corporation), a cytotoxic amphibian ribonuclease, is known to be selectively tumoricidal against cancer cells. This article briefly summarizes in vitro and in vivo tumoricidal studies of ranpirnase. It proposes mechanisms of ranpirnase based on preclinical and clinical trials. Ranpirnase significantly inhibited oxygen consumption while demonstrating improvement in several tumor physiological parameters including tumor blood flow (TBF). Ranpirnase showed chemo-sensitization with various chemotherapeutic agents in vitro and in vivo. Ranpirnase significantly reduced the tumor hypertension, the major physiological barrier of therapeutic drug delivery to solid tumors. This resulted in increased tumor penetration and selectively increased TBF. This enhanced efficacy of chemotherapeutic agents including cisplatin and doxorubicin. The possible ranpirnase-related signal transduction pathways are discussed in the context of the enhanced induction of apoptosis and inhibition of protein synthesis. As a selective cancer killer ranpirnase may be a promising candidate for improving the treatment of mesothelioma and lung cancer patients.
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Lee Intae, Kim Daehong, Lee Jihean and Shogen Kuslima, Physiological and Molecular Role of Ranpirnase on Cancer Treatment, Current Cancer Therapy Reviews 2010; 6 (1) . https://dx.doi.org/10.2174/157339410790596425
DOI https://dx.doi.org/10.2174/157339410790596425 |
Print ISSN 1573-3947 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6301 |
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Current progress in Protein Degradation and Cancer Therapy
argeted Protein Degradation is gaining momentum in cancer therapy, it facilitate targeting undruggable proteins, it overcome cancer resistance and avoid undesirable side effects. Thus small molecules degraders have emerged as novel therapeutic strategy. Targeted protein degradation (TPD), the process of eliminating a protein of interest hold a great promise for ...read more
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