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Onconase (Ranpirnase) is a chemotherapy drug derived from frog eggs that has shown antitumor activity through cell-cycle interference and apoptosis (cell death). The drug is currently in its third stage of clinical trials to determine if it is a safe and effective treatment method for patients with mesothelioma.

Fact-Checked and Updated by: Jenna Tozzi, RN

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What Is Onconase?

Chemotherapy is a class of anticancer medications that slow or stop cancer cells from replicating and infecting other parts of the body. Due to the invasive nature of mesothelioma, surgical methods are sometimes limited, which means chemotherapy is used widely to treat the disease.

Doctor speaking with a patient about Onconase

Chemotherapy treatments can vary in many ways, from how they are administered, how (and how well) they work, and their toxicity.

Currently, the first line of chemotherapy drugs used to treat mesothelioma is a mixture of pemetrexed (Alimta) and cisplatin. This drug combination has a high rate of failure due to chemoresistance (the ability of cancer cells to dodge treatment) or the presence of advanced disease.

For these reasons, new chemotherapy drugs and treatment combinations are being tested to increase survival rates and life expectancy in mesothelioma cases. One drug that shows promise is Onconase (Ranpirnase).

Onconase belongs to the pancreatic ribonuclease superfamily. It is an enzyme derived from oocytes (early embryos) of northern leopard frogs (Rana pipiens) that breaks down RNA (a type of genetic material).

Onconase is given to mesothelioma patients participating in clinical trials who do not qualify for surgical removal of malignant tumors.

Onocase cancer therapy has been seen to reduce cell replication and spread and result in cytotoxic (cell death) effects. It interferes with cell-cycle regulation, which is the process by which cells divide and replicate, and induces programmed cell death (apoptosis).

The drug is currently in its third phase of clinical trials to determine if it a safe and effective treatment method for mesothelioma in comparison to chemotherapy drugs.

If you or someone you love is undergoing treatment for mesothelioma, our Mesothelioma Survivors Guide is required reading. Inside, 7 mesothelioma survivors share practical advice about the road ahead and tell how they stayed positive.

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How Is Onconase Administered?

Onconase is given through intravenous (IV) therapy in 30-minute intervals. If the disease does not progress, the treatment is administered on a 21-day cycle (every 3 weeks) for at least 6 rounds.

Following round 6, Onconase may be used as maintenance therapy for patients who are responding well to treatment.

Onconase has been given with doxorubicin, a commonly prescribed chemotherapy drug for numerous types of malignancies (cancerous tumors), including mesothelioma.

Onconase dosage is being investigated through in vitro studies using cells that are grown in a lab and studies using mice cells.

How Does Onconase Treat Mesothelioma?

Onconase is currently being tested for widespread use in the treatment of mesothelioma.

Onconase has been found to treat mesothelioma in 4 different ways:

  1. Inhibiting production of NF-κB (a protein complex that causes healthy cells to turn cancerous)
  2. Inhibiting the ability of mesothelioma cells to spread
  3. Inducing the death of tumor cells
  4. Reducing tumor burden (size of the tumor)

Inhibiting Production of NF-κB

Asbestos harms mesothelial cells, a cellular lining found in the chest, abdomen, and heart, and leads to secretion of a gene called TNF-α.

The gene causes cells to mutate by moving a transcription factor (the script for DNA replication) called NF-κB. This, in turn, leads to the survival of the mesothelial cells but as epithelioid, sarcomatoid, or biphasic mesothelioma cell types.

Onconase treats mesothelioma by blocking the movement of the NF-κB transcription factor, causing mesothelial cells to die instead of becoming cancerous.

Inhibiting Mesothelioma Cell Invasiveness

Cell invasiveness relates to cell movement and impacts its ability to enter the extracellular matrix (the protective barrier) of neighboring tissue.

The invasive nature of a cancer cell can determine how fast cancer is able to spread throughout the body. By blocking NF-κB activity, Onconase inhibits the secretion of MMP9, a type of protein that is involved in the breakdown of the extracellular matrix. As a result, it prohibits mesothelioma invasiveness.

Getting treatment for mesothelioma? Request your Free Mesothelioma Survivors Guide and learn how 7 mesothelioma patients became mesothelioma survivors with the help of life-extending treatments.     

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Inducing Cell Death

Many chemotherapeutics cause apoptosis (cancer cell death). Studies have shown that Onconase is able to treat mesothelioma through early and late apoptosis, with increased cell death occurring with increased dosage.

Reducing Tumor Burden

Tumor burden refers to the size of the tumor, or number of cells that make up a particular mass.

Studies showed decreased tumor burden when treated with Onconase, with tumors from treated mice resuming growth after discontinuation of treatment.

This means that Onconase has a very strong antitumor effect, with this effect lasting long term.

Onconase Drug Combinations

Chemotherapy works best when drugs are given in combination. Each drug works to treat cancer cells in a different way.

When chemotherapy drugs are combined, doctors can administer each drug at its optimal dose, reducing negative side effects and the chance of chemoresistance.

Currently, Onconase is being combined with doxorubicin and dihydroartemisinin for mesothelioma treatment.

Did You Know?

Clinical trial results are showing that Onconase and doxorubicin is a safe and effective treatment in unresectable mesothelioma (mesothelioma that cannot be treated through surgery). The combination has shown a positive impact on patient survival compared to doxorubicin alone.

Onconase and dihydroartemisinin are being studied through in vitro and animal research. Results from this drug combination are promising in tumor preventative treatments, which attempt to induce tumors into a dormant (inactive) state.

Looking for more information about mesothelioma treatments and clinical trials? Connect with a mesothelioma specialist near you by using our Free Doctor Match.

Current Onconase Clinical Trials

Clinical trials are used to test the effectiveness and safety of different drugs for various forms of disease. They also give diagnosed individuals a chance to take part in research that has the potential to improve their health and overall disease prognosis.

Clinical trials are done in 4 phases:

  1. Phase I—An experimental drug is tested on a small group of people for the first time to test its safety and any possible side effects.
  2. Phase II—The drug is given to a larger group of people to gain data on the effectiveness of the drug on a particular disease or condition.
  3. Phase III—The drug is given to an even larger group to confirm its effectiveness.
  4. Phase IV—Information is gathered on the drug’s long-term benefits and risks after the drug is approved and on the market.

Onconase has been used in phase I and phase II mesothelioma trials and is currently in phase III. This randomized phase III trial is comparing the effectiveness of Onconase and doxorubicin versus doxorubicin alone in treating patients aged 21 and older with mesothelioma.

Results are showing that combining Onconase and doxorubicin may lead to improved survival rates in patients diagnosed with mesothelioma.

As part of the confirmatory stage of phase III, the U.S. Food and Drug Administration (FDA) has given Onconase orphan and fast-track drug status. This designation allows Alfacell (the company running the clinical trial) to be awarded seven years of marketing the drug for treatment of malignant mesothelioma.

Scientists continue to research the use of Onconase and other drugs derived from animals and plants to treat mesothelioma and other diseases. However, as of 2022, Onconase is the only ribonuclease with an orphan and fast-track drug status granted by the FDA.

Onconase Side Effects

As with all chemotherapy drugs, Onconase can cause negative side effects.

There is a chance that some patients may experience severe side effects, and in these cases, patients should tell their doctors immediately. Because of cytostatic function (inhibition of cell growth), Onconase is showing minimal side effects, as it does not affect healthy cells.

There are no current clinical trials where Onconase is being administered on its own.

In the phase III clinical trial described above, when combining Onconase and doxorubicin, the most common side effects patients experienced included:

  • Chills
  • Diarrhea
  • Partial or total loss of muscle movement
  • Weakness
  • Weight loss

Further side effects may be observed as scientists continue to study the drug.

Learn how 7 mesothelioma survivors handled treatment side effects — request your Free Mesothelioma Survivors Guide now.

Onconase FAQs

What is Onconase used to treat?

Onconase (Ranpirnase) is being used in clinical trials to treat patients with different types of cancer, including malignant plural or peritoneal mesothelioma.

Researchers are also looking into the use of Onconase to treat small-cell lung cancer and leukemia.

The drug is also being tested as an antiviral treatment for:

  • HIV (human immunodeficiency virus)
  • HPV (human papillomavirus)
  • Influenza
  • SARS (severe acute respiratory disease)

Has Onconase received FDA approval?

No, the FDA has not approved Onconase as a treatment for mesothelioma.

However, the FDA has given it orphan drug status. That means that the drug has shown promise in treating a rare disease.

Currently, Onconase is being used in clinical trials to treat patients with mesothelioma and other illnesses.

To date, the FDA has not approved Onconase to treat any disease.

Jenna TozziWritten by:

Director of Patient Advocacy

Jenna Tozzi, RN, is the Director of Patient Advocacy at Mesothelioma Hope. With more than 15 years of experience as an adult and pediatric oncology nurse navigator, Jenna provides exceptional guidance and support to mesothelioma patients and their loved ones. Jenna has been featured in Oncology Nursing News and is a member of the Academy of Oncology Nurse & Patient Navigators & the American Nurses Association.

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  1. Oncogene. “Onconase mediated NFKβ downregulation in malignant pleural mesothelioma”
    Retrieved from: Accessed on December 5, 2022.

  2. Genes Cancer. “Ranpirnase Interferes with NF-κB Pathway and MMP9 Activity, Inhibiting Malignant Mesothelioma Cell Invasiveness and Xenograft Growth.” Retrieved from: Accessed on December 5, 2022.

  3. US National Library of Medicine— “ONCONASE Plus Doxorubicin”
    Retrieved from: Accessed on December 5, 2022.

  4. Acta Biochim Biophys Sin (Shanghai), “Combination of onconase and dihydroartemisinin synergistically suppresses growth and angiogenesis of non-small-cell lung carcinoma and malignant mesothelioma.” Retrieved from: Accessed on December 5, 2022.

  5. Journal of Clinical Oncology. “Randomized, multicenter phase III study of ranpirnase plus doxorubicin (DOX) versus DOX in patients with unresectable malignant mesothelioma (MM).” Retrieved from: Accessed on December 5, 2022.

  6. Siraj, Y. “Promises of eukaryotic ribonucleases for cancer treatment: a systematic review.” transl med commun 7, 5 (2022). Retrieved from: Accessed on December 5, 2022.

  7. Sun, M., Sun, L., Sun, D. et al. “Targeted delivery of immuno-RNase may improve cancer therapy.” Cancer Cell International 18, 58 (2018). Retrieved from: Accessed on December 5, 2022.

  8. GlobeNewswire. “Orgenesis Completes Acquisition of Tamir Biotechnology, Inc. Assets Including Broad Spectrum Antiviral Platform.” Retrieved from: Accessed on December 5, 2022.

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