Targeting PTPRK-RSPO3 colon tumours promotes differentiation and loss of stem-cell function
Menée in vitro et in vivo, cette étude met en évidence des mécanismes suggérant l’intérêt d’une thérapie ciblée sur RSPO3 pour le traitement de patients atteints d’une tumeur du côlon présentant une fusion des gènes PTPRK et RSPO3
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.