Abstract
A novel approach of antitumor treatment, that involves targeting RNA either using specific antisense oligonucleotides or cytostatic/cytotoxic ribonucleases (RNases), is being promoted. Among recently described cytotoxic RNases, amphibian RNases, including ranpirnase (onconase; ONC) and Amphinase (rAmph), are promising anticancer agents. They manifest strong antitumor effects and act synergistically with several cytostatics. Recently, rapidly developed proteins by engineering of RNases, displayed cytotoxic activity against several types of malignant cells. Most recent data show the role of microRNAs in mediating tumor progression, opening a new field of possible molecular targets for RNases. This review summarizes the current status of those RNases and immunoRNases as promising novel anticancer therapeutics.
Highlights
Antitumor ribonucleases (RNases) are a promising superfamily of small (10-28 kDa) basic proteins with strong cytotoxic and cytostatic potential on cancer cells [1]
This review summarizes the current status of those RNases and immunoRNases as promising novel anticancer therapeutics
This group of secretory enzymes operates at the crossroads of transcription and translation, preferentially degrading tRNA, and as a result, lead to inhibition of protein synthesis
Summary
Antitumor ribonucleases (RNases) are a promising superfamily of small (10-28 kDa) basic proteins with strong cytotoxic and cytostatic potential on cancer cells [1]. We describe structures, functions and mechanisms of antitumor activity of RNases with particular emphasis to the amphibian ONC and Amp. The advancements of recombinant technology have allowed the assembly and conjugation of RNases with monoclonal antibodies, investigated in a variety of human malignancies both in vitro and in animal models. Such combinations called immunoribonucleases (immunoRNases) internalize tumor-targeting and has demonstrated selective antitumor activity against cancer cell [5].
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