Experimental Drug Added to Chemotherapy May Significantly Reduce Sarcoma Tumors
Researchers with Moffitt Cancer Center and the University of South Florida have found that a two-drug combination consisting of an experimental drug by Merck and the chemotherapy agent gemcitabine can significantly reduce sarcoma tumor volume compared to receiving one drug or the other. The research was recently published in the journal PLOS ONE.
Sarcoma is a rare group of cancers that begin in the tissues that support and connect the body, such as bone, fat cells, muscle, nerves, tendons, the lining of joints, blood vessels or lymph vessels. Both adults and children can develop a sarcoma, but sarcoma tumors account for a greater number of pediatric cancers than adult, says lead author of the most recent study, Soner Altiok MD PhD, an associate member of Moffitt’s Chemical Biology and Molecular Medicine Program.
Unfortunately, sarcoma cancer response rates to standard chemotherapies have been low, so there is a need for new drugs to improve overall survival.
MK-1775 is an experimental drug that inhibits Wee 1, a protein known to regulate cell size and initiate cell division, an important step in the development of sarcoma. Inhibition of Wee 1 by MK-1775 has been shown to induce cell death in sarcoma tumors. The drug even appears to work if the patient has p53 gene mutation, which is a common mutation found in cancer cells and is present in over 50% of cancers.
However, as a single agent, MK-1775 was not effective in all cancers, so the researchers at Moffitt studied the synergistic effect of combining the experimental drug with a standard chemotherapy drug, gemcitabine. The combination resulted in a 70% decrease in tumor volume when compared to receiving one drug or the other – gemcitabine alone inhibiting 40% of tumor growth; MK-1775 alone inhibiting 50% of growth.
"The combination of MK-1775 and gemcitabine demonstrated a synergistic effect in sarcoma cells," explained Altiok. "MK-1775 alone caused tumor cell damage, but when used in combination with gemcitabine, there was increased cell death." Altiok also notes that MK-1775 is a well-tolerated, readily available targeted drug.
Currently, there are 4 active clinical trials testing MK-1775 in various cancer types, per the National Cancer Institute.
Jenny M. Kreahling, Parastou Foroutan, Damon Reed, Gary Martinez, Tiffany Razabdouski, Marilyn M. Bui, Meera Raghavan, Douglas Letson, Robert J. Gillies, Soner Altiok.Wee1 Inhibition by MK-1775 Leads to Tumor Inhibition and Enhances Efficacy of Gemcitabine in Human Sarcomas. PLoS ONE, 2013; 8 (3): e57523 DOI:10.1371/journal.pone.0057523
Cancer.Net (American Society of Clinical Oncology) – Sarcoma
National Cancer Institute – WEE1 inhibitor MK-1775