Oss – Amsterdam, July 10th, 2015 – Researchers from the Netherlands Cancer Institute (NKI), in collaboration with NTRC and University Medical Center Utrecht, have discovered that inhibition of the protein kinase TTK, a protein involved in chromosome segregation, increases the efficacy of taxane chemotherapy in models of triple-negative breast cancer. The results of these pre-clinical studies have been published in a research article in Annals of Oncology, which appeared online this week.
Triple-negative breast cancers are considered the most aggressive type of breast cancer, for which no targeted therapy exists at the moment. These tumors are characterized by a high degree of chromosome instability and often overexpress the spindle assembly checkpoint kinase TTK. This observation led prof. Dr. Rene Medema (NKI) and his team to investigate the potential of TTK inhibition as a targeted therapy for triple-negative breast cancer. A very potent and highly selective small molecule inhibitor of TTK, developed at NTRC, was tested in various pre-clinical models. Combination of the inhibitor with a therapeutic dose of docetaxel resulted in extended tumor remission. Most likely the two compounds act synergistically. Therefore, the researchers propose TTK inhibition as an add-on to current therapies for triple-negative breast cancer.To further study the mechanism of action and the potential application of TTK in other tumors, Rene Medema recently received a grant from the Dutch Cancer Society (KWF). The collaboration with NTRC and UMCU has been extended in a program funded by the European Commission (‘PloidyNet’), in a consortium involving also other expert research groups in the field of aneuploidy.
Reference: Maia et al. (2015) Inhibition of the spindle assembly checkpoint kinase TTK enhances the efficacy of docetaxel in a triple negative breast cancer model, published online first 7 July 2015
NTRC is a precision medicine company dedicated to the development of new anti-cancer drugs. NTRC facilitates the development of novel therapies by providing cancer cell line profiling services (Oncolines™ and SynergyFinder™) and developing new enabling technologies, such as NFK GreenScreen™. In addition, NTRC develops own novel targeted therapies based on small molecules, such as selective inhibitors of TTK (Mps1) protein kinase for chromosomal unstable tumors and inhibitors of the tryptophan metabolizing enzymes IDO1 and TDO for cancer immunotherapy.