Journal
NATURE
Volume 529, Issue 7584, Pages 97-+Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nature16466
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Colorectal cancer remains a major unmet medical need, prompting large-scale genomics efforts in the field to identify molecular drivers for which targeted therapies might be developed(1-3). We previously reported the identification of recurrent translocations in R-spondin genes present in a subset of colorectal tumours(4). Here we show that targeting RSPO3 in PTPRK-RSPO3-fusion-positive human tumour xenografts inhibits tumour growth and promotes differentiation. Notably, genes expressed in the stem-cell compartment of the intestine were among those most sensitive to anti-RSPO3 treatment. This observation, combined with functional assays, suggests that a stem-cell compartment drives PTPRK-RSPO3 colorectal tumour growth and indicates that the therapeutic targeting of stem-cell properties within tumours may be a clinically relevant approach for the treatment of colorectal tumours.
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