Signaling Resistance

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

Jenny Rood
Apr 1, 2015

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

EDITOR'S CHOICE IN CELL & MOLECULAR BIOLOGY

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...

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