BMTP-11 found to delay progression of osteosarcoma
Osteosarcoma is a rare but aggressive tumor that affects the bone. The overall incidence of osteosarcoma is low. But it is the most frequent cause of cancer mortality among children and young adults. If osteosarcoma is localized, the five-year survival rate is about 60–65%. If the disease has spread to other parts of the body, the five-year survival rate is only 20–25%. Over the last 25 years, these survival rates have remained essentially unchanged. Treatment options for osteosarcoma are limited and may cause adverse effects.
Now a research team consisting of scientists from the University of Texas M.D. Anderson Cancer Center, University of New Mexico Comprehensive Cancer Center, University of Michigan Comprehensive Cancer Center, and Harvard Medical School has identified a marker of osteosarcoma progression and poor prognosis. The study, detailed in the Proceedings of the National Academy of Sciences, reveals that the IL-11 receptor α subunit (IL-11Rα) and its ligand IL-11 are increased in human metastatic osteosarcoma cell lines, and this enhances the growth, proliferation, and invasion of tumor cells in vitro and promotes the formation of lung metastases in vivo. These results indicate that IL-11Rα may act as a marker of disease progression and poor prognosis in patients with osteosarcoma and targeting IL-11Rα may be an approach to inhibit osteosarcoma metastasis.
Previous studies have revealed a potential link between the IL-11:IL-11Rα axis and osteosarcoma. In this work, the team further explored this axis' role. Using multiple analytic methods like immunohistochemistry (IHC), the team measured the levels of IL-11Rα expression in tissue samples from osteosarcoma patients and found that IL-11Rα levels in metastases were much higher than that in primary tumors. Correlation studies showed that patients who had higher IL-11Rα in their primary tumors were more likely to have a worse prognosis. Further investigation revealed that IL-11, the ligand of IL-11Rα, was expressed at higher levels in metastatic cell lines than in nonmetastatic cells. Collectively, these findings support the potential of IL-11Rα as a biomarker of progression of osteosarcoma.
Next, the team tested the effect of an IL-11Rα-targeting drug, called BMTP-11, in a orthotopic model of human metastatic osteosarcoma. Results showed that BMTP-11 delayed primary tumor growth and secondary metastatic spread of human osteosarcoma cells in the animals. Furthermore, this effect was enhanced when BMTP-11 was used in combination with the chemotherapy medication gemcitabine. BMTP-11 is still in development, and more research is needed to evaluate its efficacy in osteosarcoma.
Overall, the study supports that targeting IL-11Rα may be a therapeutic intervention for osteosarcoma and underscores the potential of BMTP-11 as a therapeutic agent for osteosarcoma. Valerae Lewis, first author of the study and a researcher at the University of Texas M.D. Anderson Cancer Center, noted that BMTP-11 attacks the tumor without affecting other tissues.
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