Research Identifies Important Proteins that Play Role in Sarcoma Cancer Growth
Sarcomas are rare forms of cancer which arise from bone, fat, muscle or vascular tissues. Currently there are no approved drugs for treatment of sarcoma in the United States, although one from GlaxoSmithKline is awaiting FDA approval. Votrient (pazopanib) belongs to a class of medications called tyrosine kinase inhibitors which works by slowing or stopping the spread of cancer cells. These tyrosine kinases are the focus of new research for potential new treatments of sarcoma by scientists at Moffitt Cancer Center.
Study leader Eric B. Haura MD, program leader for Experimental Therapeutics hypothesized that tyrosine kinases play a significant role in a wide range of cellular processes which is commonly disrupted in diseases such as cancer. These enzymes transfer phosphate groups from ATP (a chemical energy structure in cells) to a protein which can turn the cell “on” or “off.” When protein kinases become mutated, they can be stuck in the “on” position, which causes unregulated cell growth as seen in cancer.
Regarding sarcoma cancers, the proteins that drive growth and survival in this rare disease is poorly understood. Dr. Haura and his team used mass spectrometry to identify 1,936 unique tyrosine phosphorylated peptides corresponding to 844 unique phosphor-tyrosine proteins and found 39 tyrosine kinases in sarcoma cells.
Right now, it is unknown if any of these tyrosine kinases identified in sarcoma tumor cell lines act to regulate tumor cell growth and tumor survival. However, further studies can help prioritize which target might be useful for potential pharmaceutical agents to treat those with sarcoma cancers. "Tyrosine kinases play an important role in controlling the hallmarks of cancer, and they have a proven track record as druggable targets for cancer treatment,” said Dr. Haura.
He concludes, "We think this approach could hold promise in profiling tumors directly from patients and can complement existing genetic data on sarcomas. Our results show this is feasible in tumor tissues, and we hope to advance this further by directly studying additional tumors from sarcoma patients."
Y. Bai, J. Li, B. Fang, A. Edwards, G. Zhang, M. Bui, S. Eschrich, S. Altiok, J. Koomen, E. B. Haura.Phosphoproteomics identifies driver tyrosine kinases in sarcoma cell lines and tumors. Cancer Research, 2012; DOI: 10.1158/0008-5472.CAN-11-3015
American Association for Cancer Research