Onconase , sometimes known as Ranpirnase or P-30 protein, is a chemotherapeutic agent, still in Phase III clinical trials, that has shown some success in the treatment of mesothelioma that don’t respond to more conventional chemotherapeutic agents like Alimta®, cisplatin and carboplatin. Onconase is a stable endoribonuclease derived from an enzyme found in the eggs and embryonic stem cells of the northern leopard frog. The enzyme’s mechanism is not entirely understood but is thought to be a catalyst in the enzymatic breakdown of RNA within the tumor cell that results in the suppression of protein synthesis, thereby effectively halting the metastasis process. Onconase has proven to have some effectiveness in fighting other types of cancer besides mesothelioma, notably leukemia and breast cancer.
How It Works
Onconase works by triggering several events simultaneously within the affected tumor cell. Initially the enzyme binds to receptors on the surface of the tumor cell. From there it is absorbed into the tumor cell’s intracellular fluid (cytosol) through endocytosis, giving it access to endogenous ribonuclease inhibitors throughout the cell with which it works to degrade RNA. Onconase inhibits protein synthesis, inhibits cell growth and proliferation, and accelerates the natural process of apoptosis.
Clinical trials study the treatment of patients with new or experimental drugs that medical experts have good reason to believe will be effective against specific diseases. There are three phases to the clinical trial process. In Phase I, the objective is to find out how much of the experimental drug can be administered safely (dosage), and to determine the side effects. In Phase II, patients are carefully monitored to see what, if any, specific cancer fighting properties the experimental drug has. Phase III, or advanced, clinical trials determine both the therapeutic and side effects of the experimental medication on large numbers of patients, comparing its effectiveness to the effectiveness of more standard medications for the same condition (control group) and often against the effectiveness of no treatment at all (control group).
The U.S. Food and Drug Administration (FDA) was impressed enough with the results of early Onconase mesothelioma trials to grant it orphan drug status, thereby allowing it to go into advanced clinical trials sooner than is the case with most new chemotherapeutic agents. “Orphan drug” is a designation given to pharmaceuticals that have been specifically developed to combat rare diseases. Drugs like Onconase could one day be added to standard treatment regimens for diseases such as mesothelioma.