Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
Sci. Signal., 21 September 2010
Vol. 3, Issue 140, p. ra67
Rationally Designing Combination Therapy
Drug resistance is a problem in cancer treatment, making combination therapies common. However, all too often, resistance also develops to empirically developed combination therapies, or those combinations are generally cytotoxic and not selective for the cancer cells. Astsaturov et al. developed a library of candidate genes centered on the epidermal growth factor receptor (EGFR) and targeted these genes with silencing RNAs to identify candidate proteins that could be inhibited to reduce cancer cell viability in the presence of EGFR inhibitors. Cotreatment with EGFR inhibitors and clinically available drugs that inhibit the candidate proteins reduced tumor size in xenografts and cell viability of multiple cancer cell lines. These results suggest that this network-centered approach may be fruitful for development of rationally designed combination therapies.
Citation: I. Astsaturov, V. Ratushny, A. Sukhanova, M. B. Einarson, T. Bagnyukova, Y. Zhou, K. Devarajan, J. S. Silverman, N. Tikhmyanova, N. Skobeleva, A. Pecherskaya, R. E. Nasto, C. Sharma, S. A. Jablonski, I. G. Serebriiskii, L. M. Weiner, E. A. Golemis, Synthetic Lethal Screen of an EGFR-Centered Network to Improve Targeted Therapies. Sci. Signal.3, ra67 (2010).
Elizabeth M. Adler and Nancy R. Gough (29 March 2011) Sci. Signal.4 (166), eg3.
[DOI: 10.1126/scisignal.2002014] |Abstract »|Full Text »|PDF »
Nancy R. Gough and Michael B. Yaffe (15 February 2011) Sci. Signal.4 (160), eg2.
[DOI: 10.1126/scisignal.2001871] |Abstract »|Full Text »|PDF »
Michael B. Yaffe and Annalisa M. VanHook (4 January 2011) Sci. Signal.4 (154), pc1.
[DOI: 10.1126/scisignal.2001786] |Abstract »|Full Text »|Podcast »
Birgit Schoeberl, Emily A. Pace, Jonathan B. Fitzgerald, Brian D. Harms, Lihui Xu, Lin Nie, Bryan Linggi, Ashish Kalra, Violette Paragas, Raghida Bukhalid, Viara Grantcharova, Neeraj Kohli, Kip A. West, Magdalena Leszczyniecka, Michael J. Feldhaus, Arthur J. Kudla, and Ulrik B. Nielsen (30 June 2009) Sci. Signal.2 (77), ra31.
[DOI: 10.1126/scisignal.2000352] |Editor's Summary »|Abstract »|Full Text »|PDF »|Supplementary Materials »
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Targeting C4-Demethylating Genes in the Cholesterol Pathway Sensitizes Cancer Cells to EGF Receptor Inhibitors via Increased EGF Receptor Degradation.
A. Sukhanova, A. Gorin, I. G. Serebriiskii, L. Gabitova, H. Zheng, D. Restifo, B. L. Egleston, D. Cunningham, T. Bagnyukova, H. Liu, et al. (2013)
|Abstract »|Full Text »|PDF »
Tankyrase and the Canonical Wnt Pathway Protect Lung Cancer Cells from EGFR Inhibition.
M. Casas-Selves, J. Kim, Z. Zhang, B. A. Helfrich, D. Gao, C. C. Porter, H. A. Scarborough, P. A. Bunn Jr., D. C. Chan, A. C. Tan, et al. (2012)
|Abstract »|Full Text »|PDF »
Computational Approaches for Analyzing Information Flow in Biological Networks.