Ribonucleases as a Novel Pro-Apoptotic Anticancer Strategy: Review of the Preclinical and Clinical Data for Ranpirnase
Monday, November 28th, 2005.
Cancer Investigation. 2005;23(7):643-650. [Link]
Costanzi J, Sidransky D, Navon A, Goldsweig H.
Lone Star Oncology, Lone Star Oncology, Austin, Texas, USA.
Abstract
Cytotoxic ribonucleases (RNases), such as ranpiranase, represent a novel mechanism-based approach to anticancer therapy. These relatively small proteins selectively attack malignant cells, triggering apoptotic response and inhibiting protein synthesis. Ranpirnase, originally isolated from oocytes of Rana pipiens, is a member of a family of endoribonucleases. The anticancer effects of ranpiranase have been documented in both in vitro and in vivo experimental tumor models. The effects of ranpiranase appear to be selective for cancer cells. Based on Phase I study data, the maximum tolerated dose (MTD) was 960 microg/m(2), with the dose-limiting toxicity (DLT) characterized by proteinuria with or without azotemia, peripheral edema, and fatigue. Ranpirnase did not induce myelosuppression, mucositis, alopecia, cardiotoxicity, coagulopathy, hepatotoxicity, or adverse metabolic effects. Phase II tumor-specific trials investigated the activity of ranpirnase in malignant mesothelioma, breast cancer, non-small cell lung cancer, and renal cell cancer. A Phase III randomized study in malignant mesothelioma patients compares the combination of ranpirnase plus doxorubicin to doxorubicin monotherapy.
Glossary
- alopecia
- (al-o-pee-shuh) hair loss. This often occurs as a result of chemotherapy or, less often, from radiation therapy to the head. In most cases, the hair grows back after treatment ends.
- therapy
- any of the measures taken to treat a disease. Unproven therapy is any therapy that has not been scientifically tested and approved. Use of an unproven therapy instead of standard (proven) therapy is called alternative therapy. Some alternative therapies have dangerous or even life-threatening side effects. For others, the main danger is that a patient may lose the opportunity to benefit from standard therapy. Complementary therapy, on the other hand, refers to therapies used in addition to standard therapy. Some complementary therapies may help relieve certain symptoms of cancer, relieve side effects of standard cancer therapy, or improve a patient's sense of well-being. The ACS recommends that patients considering use of any alternative or complementary therapy discuss this with their health care team.
- oncology
- (on-call-o-jee) the branch of medicine concerned with the diagnosis and treatment of cancer.
- mucositis
- (mu-co-site-us) inflammation of a mucous membrane such as the lining of the mouth.
- edema
- (eh-deem-uh) build-up of fluid in the tissues, causing swelling. Edema of the arm can occur after radical mastectomy, axillary dissection of lymph nodes, or radiation therapy.
- cytotoxic
- (site-o-tox-ik) toxic to cells; cell-killing.
- cell
- the basic unit of which all living things are made. Cells replace themselves by splitting and forming new cells (mitosis). The processes that control the formation of new cells and the death of old cells are disrupted in cancer.
- cancer
- malignancy; a group of diseases typified by abnormal, generally out-of-control, cell growth.
- tumor
- an abnormal lump or mass of tissue. Tumors can be benign (not cancerous) or malignant (cancerous).
- mesothelioma
- a tumor derived from mesothelial tissue, such as the peritoneum (lining the abdomen) or pleura (lining the lungs). More on mesothelioma.
