Research ArticleCancer Biology

Synthetic Lethal Screen of an EGFR-Centered Network to Improve Targeted Therapies

Sci. Signal.  21 Sep 2010:
Vol. 3, Issue 140, pp. ra67
DOI: 10.1126/scisignal.2001083

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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.