Targeting PTPRK-RSPO3 colon tumours promotesdifferentiation and loss of stem-cell function

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 proteins 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 tumors.EGA study EGAS00001001462