Researchers at Moffitt Cancer Center and colleagues at the University of South Florida have found that when given together, a two-drug combination acts synergistically in test animals modeled with sarcoma tumors. They report that the drug combination of MK-1775 and gemcitabine resulted in a 70 percent decrease in the tumor volume when compared to receiving one drug or the other.
Their study was published in the March 8 online edition of PLOS ONE.
"Sarcomas are rare tumors affecting both children and adults, but sarcomas account for a greater number of pediatric cancers than adult," said study lead author Soner Altiok, M.D., Ph.D., associate member of the Chemical Biology and Molecular Medicine Program. "Sarcoma response rates to standard chemotherapies have been low, drug toxicity has been high, and improvement in overall survival, especially in metastatic disease, has been negligible. New drugs are needed."
Sarcomas are cancers that result from transformed cells in one of a number of tissues, including bone, cartilage, fat, muscle and vascular tissues. Sarcomas are different from carcinomas, such as breast, colon and lung cancers.
Researchers from Moffitt's Chemical Biology and Molecular Medicine and Sarcoma programs had previously collaborated in testing MK-1775's ability to inhibit Wee1, a protein known to regulate cell size and initiate cell division, an important step in the development of sarcoma. Wee1 plays a role in determining the time at which cell division begins. The researchers found that inhibition of Wee1 by MK-1775 induced cell death in sarcoma tumors.
"Inhibition of the pathways critical to tumor cell survival by molecularly targeted therapy represents an opportunity to reverse the biological basis of tumor formation," Altiok explained.
To further prove that inhibition of Wee1 by MK-1775 leads to cell death in sarcomas cells, the researchers performed additional studies, including s
|Contact: Kim Polacek|
H. Lee Moffitt Cancer Center & Research Institute