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| From OncoLog,
May 2009, Vol. 54, No. 5 |
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Overexpressed Protein Could Be Targeted in Osteosarcoma
A protein known to be highly expressed in bone metastases is also active in osteosarcomas, M. D. Anderson researchers have discovered. The finding suggests that osteosarcomas may be treatable with therapeutic agents that shut down the protein, known as interleukin-11 receptor alpha (IL-11–alpha).
Using a mouse model, the researchers determined that IL-11–alpha was present at high levels in primary osteosarcomas and osteosarcomas that had spread to the lungs. However, the protein was absent from normal bone and lung tissues. Immunohistochemical staining of human tissues provided further evidence that IL-11–alpha is highly expressed in primary and metastatic osteosarcomas as well as the blood vessels feeding them.
To test whether osteosarcomas in the mice would take up therapy targeting IL-11–alpha, the researchers intravenously administered phages (virus-like particles) containing an IL-11–alpha ligand. The phages were selectively taken up by the tumors but not healthy tissue. “Our findings indicate that therapeutic targeting of IL-11–alpha may yield anti-tumor, anti-metastasis, and anti-angiogenesis effects in osteosarcoma,” said Valerae O. Lewis, M.D., the study’s senior author and associate professor and chief of the Department of Orthopedic Oncology at M. D. Anderson. The findings, published in the journal Cancer Research, are also important because researchers have identified very few proteins in primary osteosarcoma that might be targeted by therapeutic agents.
Finding an effective molecularly targeted therapy for osteosarcoma, the most common primary tumor of the bone, would be a long-needed breakthrough in treatment. Current chemotherapeutic agents for osteosarcoma are toxic to the nerves, heart, kidneys, and auditory system, which limits their use. About 30% of osteosarcoma patients die from the disease.
A therapeutic agent targeting interleukin receptor expression is now undergoing preclinical testing in osteosarcoma. Investigators hope the agent, developed at M. D. Anderson and named BMTP-11, shows efficacy against primary bone tumors and can quickly be moved to clinical testing. BMTP-11 will also soon begin phase I clinical testing in patients with bone metastases from prostate cancer. Preclinical testing showed that the agent induced cell death in such metastases.
For more information on this topic or for questions about M. D. Anderson’s treatments, programs, or services, call askMDAnderson at (877) MDA-6789.
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