生物谷報道：新研究提出一個也許能改進一類抗癌新藥效果的方法,。這些被稱為“靶向治療”(targetedtherapies)的藥物通過抑制單個受體酪氨酸蛋白激酶(RTKs)的活性而起作用,，RTKs是幫助驅(qū)動癌細胞失控生長的信號發(fā)生蛋白質(zhì)。這類療法在臨床試驗中顯示了可觀的前景,，但是某些固體腫瘤,，包括一種侵犯性強的腦瘤——多形性膠質(zhì)母細胞瘤，對療法的反應(yīng)不理想,。JayneStommel和同事用動物腫瘤模型的實驗發(fā)現(xiàn),，許多不同的RTKs在多形性膠質(zhì)母細胞瘤中過度激活，如果不是針對一個RTK的單一藥物,，而用針對多個RTKs的藥物組合來治療腫瘤,，療效要更好。這個方法對人類腫瘤的效果可以用臨床試驗來檢驗,。（科學(xué)時報）
原始出處:
Published Online September 13, 2007
Science DOI: 10.1126/science.1142946
Submitted on March 23, 2007
Accepted on August 31, 2007
Coactivation of Receptor Tyrosine Kinases Affects the Response of Tumor Cells to Targeted Therapies
Jayne M. Stommel 1, Alec C. Kimmelman 1, Haoqiang Ying 1, Roustem Nabioullin 1, Aditya H. Ponugoti 1, Ruprecht Wiedemeyer 1, Alexander H. Stegh 1, James E. Bradner 1, Keith L. Ligon 1, Cameron Brennan 2, Lynda Chin 1, Ronald A. DePinho 1*
1 Departments of Medical Oncology, Medicine, Dermatology, Pathology, and Genetics, Belfer Institute, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02115, USA.
2 Department of Neurosurgery, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA.
* To whom correspondence should be addressed.
Ronald A. DePinho , E-mail: [email protected]
Targeted therapies that inhibit receptor tyrosine kinases (RTKs) and the downstream phosphatidylinositol 3-kinase (PI3K) signaling pathway have shown promising anti-cancer activity, but their efficacy in the brain tumor glioblastoma multiforme (GBM) and other solid tumors has been modest. We hypothesized that multiple RTKs are co-activated in these tumors and that redundant inputs drive and maintain downstream signaling, thereby limiting the efficacy of therapies targeting single RTKs. Tumor cell lines, xenotransplants, and primary tumors indeed show multiple concomitantly activated RTKs. Combinations of RTK inhibitors and/or RNAi, but not single agents, decreased signaling, cell survival, and anchorage-independent growth even in glioma cells deficient in PTEN, a frequently inactivated inhibitor of PI3K. Thus, effective GBM therapy may require combination regimens targeting multiple RTKs.
