Signaling Resistance

Activating signaling pathways, rather than individual genes, reveals roles for both growth and dedifferentiation in establishing resistance to cancer treatments.

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PATHWAYS PROBED: Researchers search for molecular pathways that allow tumor cells (shown here) to outlast anticancer drugs. MOHAMMED KOHANDEL

The paper C.A. Martz et al., “Systematic identification of signaling pathways with potential to confer anticancer drug resistance,” Science Signaling, 7:ra121, 2014. The debate Researchers have two theories about how tumor cells develop resistance to anticancer drug treatments: either through an uptick in pro-growth signals or via dedifferentiation pathways that return them to a stem-like state. Single-gene studies have provided evidence for both strategies. The screen To get a more comprehensive view of what’s happening, researchers from MIT and Duke University looked at signaling pathways, instead of individual genes. They used a library of 40 mutant cDNAs to activate or inactivate 17 cancer-related pathways in melanoma and breast cancer cell lines, then assayed the cells’ responses to 13 common targeted anticancer treatments. In addition to ...

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