CANCER BIOLOGY

Creating a safe haven for tumor cells

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Science  15 May 2015:
Vol. 348, Issue 6236, pp. 769
DOI: 10.1126/science.348.6236.769-d

Neighboring fibroblasts help cancer cells tolerate certain drugs

PHOTO: E. HIRATA ET AL. CANCER CELL 27, 4 (13 APRIL 2015) © 2015 ELSEVIER INC.

Melanomas with certain mutations often respond dramatically to drugs inhibiting a protein kinase called BRAF. This is because BRAF is part of a signaling pathway that, when mutationally activated, drives melanoma growth. Unfortunately, the response is often short-lived because tumor cells develop resistance to the drugs. Hirata et al. make the surprising observation that melanoma cells do not acquire resistance to BRAF inhibition on their own but rather receive help from neighboring fibroblasts. BRAF inhibitors cause fibroblasts to remodel the extracellular matrix. Signals from the remodeled matrix then reactivate the growth signaling pathway in the melanoma cells. Thus, the tumor microenvironment can provide a safe haven for tumor cells that allows them to tolerate certain drugs.

Cancer Cell 27, 574 (2015).

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