Synthetic lethal screening with small-molecule inhibitors provides a pathway to rational combination therapies for melanoma.

ABSTRACT: Recent data show that extracellular signals are transmitted through a network of proteins rather than hierarchical signaling pathways, suggesting that the inhibition of a single component of a canonical pathway is insufficient for the treatment of cancer. The biologic outcome of signaling through a network is inherently more robust and resistant to inhibition of a single network component. In this study, we conducted a functional chemical genetic screen to identify novel interactions between signaling inhibitors that would not be predicted on the basis of our current understanding of signaling networks. We screened over 300 drug combinations in nine melanoma cell lines and have identified pairs of compounds that show synergistic cytotoxicity. The synergistic cytotoxicities identified did n

SUBMITTER: Roller DG 

PROVIDER: S-EPMC3496043 | biostudies-literature | 2012 Nov

REPOSITORIES: biostudies-literature