[Onconase: a ribonuclease with antitumor activity]
Małgorzata Zwolińska1, Piotr Smolewski
1Klinika Hematologii Uniwersytetu Medycznego w Łodzi, Łódź.
Abstract:
Onconase (ranpirnase) is a homologous protein obtained from Rana pipiens frog eggs. The activity of onconase, and particularly its antitumor effect, is strictly connected with ribonuclease(RN-ase) activity. Onconase induces cell death through the decomposition of inner cellular RNA,inhibition of protein synthesis, and inhibition of cell growth and proliferation and it also specifically triggers tumor cell apoptosis. A very important mechanisms of its cytotoxicity is also its antioxidant activity. The results of preclinical trials demonstrated a high activity of onconase against tumor cells, also those resistant to cytostatics. Moreover, onconase showed synergic activity with other commonly used anticancer drugs. Several clinical trials were performed on patients suffering from kidney, breast, and pancreatic cancers. Most recently a phase III study of onconase in patients with mesothelioma was completed. There are also ongoing phase I and II clinical trials with non-small-cell lung cancer (NSCLC).
Insights
Onconase, a ribonuclease (RN-ase) from frog eggs, shows potent antitumor effects by inducing cancer cell death and apoptosis. It demonstrates efficacy against resistant tumors and synergistic activity with other cancer drugs.
Area of Science:
- Biochemistry
- Oncology
- Molecular Biology
Background:
- Onconase (ranpirnase) is a ribonuclease (RN-ase) enzyme derived from Rana pipiens frog eggs.
- Its antitumor activity is intrinsically linked to its RN-ase function, targeting intracellular RNA.
- Onconase exhibits cytotoxic effects via RNA decomposition, protein synthesis inhibition, and apoptosis induction in tumor cells.
Purpose of the Study:
- To evaluate the antitumor potential of Onconase.
- To investigate its mechanisms of action, including cytotoxicity and antioxidant properties.
- To assess its efficacy in preclinical models and clinical trials for various cancers.
Main Methods:
- Preclinical studies involving tumor cell lines, including those resistant to conventional chemotherapy.
- In vitro assays to determine Onconase's ribonuclease activity, cytotoxicity, and antioxidant effects.
- Clinical trials in patients with kidney, breast, pancreatic, mesothelioma, and non-small-cell lung cancer (NSCLC).
Main Results:
- Onconase demonstrated significant antitumor activity in preclinical trials, effective against cytostatic-resistant cancer cells.
- The enzyme possesses notable antioxidant properties contributing to its cytotoxicity.
- Clinical trials indicated Onconase's potential in treating various cancers, with a completed Phase III study in mesothelioma and ongoing trials for NSCLC.
Conclusions:
- Onconase is a promising anticancer agent with a unique mechanism of action involving RNA degradation and apoptosis induction.
- Its efficacy against resistant tumors and synergistic potential with other drugs warrant further clinical investigation.
- Ongoing and completed clinical trials support the therapeutic potential of Onconase in diverse oncological indications.
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