Drugs that inhibit receptor tyrosine kinases (RTKs) have emerged as promising anti-cancer therapies in clinical trials, but certain solid tumors such as glioblastoma multiforme (GBM) respond poorly to them. Work by Stommel et al. may help explain why GBM, an aggressive form of brain cancer, is so refractory to this class of drugs, which are typically administered as single agents. Glioblastoma cells display concomitant activation of multiple RTKs, all of which stimulate the phosphatidylinositol 3-kinase (PI3K) signaling pathway, a critical driver of cell growth. In preclinical models, combinations of agents targeting multiple RTKs were more powerful than single agents in inhibiting the PI3K pathway and slowing tumor cell growth. These results suggest a potential strategy for optimizing the efficacy of RTK inhibitors in GBM, an idea that can now be tested in clinical trials.
J. M. Stommel, A. C. Kimmelman, H. Ying, R. Nabioullin, A. H. Ponugoti, R. Wiedemeyer, A. H. Stegh, J. E. Bradner, K. L. Ligon, C. Brennan, L. Chin, R. A. DePinho, Coactivation of receptor tyrosine kinases affects the response of tumor cells to targeted therapies. Science 318, 287-290 (2007). [Abstract] [Full Text]