Combining a Wee1 protein inhibitor with the standard chemotherapy agent gemcitabine significantly reduced sarcoma tumor volume, and to a greater extent than seen with either drug alone.
Work by a team led by Soner Altiok, MD, PhD, of the H. Lee Moffitt Cancer Center & Research Institute in Tampa, Florida, focused on an agent known as MK-1775. MK-1775 inhibits Wee1, a protein known to regulate cell size and initiate cell division, important in the development of sarcoma. MK-1775 had previously been shown to induce cell death in sarcoma tumors by inhibiting Wee1.
In the new study, Altiok and colleagues tested the effects of MK-1775 in combination with gemcitabine in a number of sarcoma cell lines derived from patient tissues and then in laboratory animals with osteosarcoma. Gemcitabine is frequently used in the treatment of sarcomas, noted the investigators in their report for PLOS One (2013;8:e57523).
Whereas MK-1775 alone caused tumor cell damage, combining the treatment with gemcitabine increased cell death. In the lab animals, gemcitabine alone inhibited 40% of tumor growth and MK-1775 alone inhibited 50% of tumor growth. When used together, however, the drugs inhibited 70% of tumor cell growth.
The findings suggest that MK-1775, which has a high safety profile, has potential as a treatment for sarcomas in both children and adults.