Targeting PTPRK-RSPO3 colon tumours promotes differentiation and loss of stem-cell function.

Nature 2016 Jan 7

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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. We previously reported the identification of recurrent translocations in R-spondin genes present in a subset of colorectal tumours. 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.

Citation

Elaine E Storm, Steffen Durinck, Felipe de Sousa e Melo, Jarrod Tremayne, Noelyn Kljavin, Christine Tan, Xiaofen Ye, Cecilia Chiu, Thinh Pham, Jo-Anne Hongo, Travis Bainbridge, Ron Firestein, Elizabeth Blackwood, Ciara Metcalfe, Eric W Stawiski, Robert L Yauch, Yan Wu, Frederic J de Sauvage. Targeting PTPRK-RSPO3 colon tumours promotes differentiation and loss of stem-cell function. Nature. 2016 Jan 7;529(7584):97-100