New research has shown that two proteins—Slit2 (purported to be involved in cellular migration) and R-spondin 1 (a Wnt agonist)—impart a protective effect on intestinal stem cells (ISCs) in mice treated with high doses of chemoradiation. Indeed, depleting the Slit2 receptor Robo1 resulted in a reduction in ISC number and caused villus hypertrophy. By contrast, administration of R-spondin 1 and Slit2 mitigated ISC loss after chemoradiation in mice. Importantly, manipulating the levels of these proteins did not adversely affect the sensitivity of tumours in ApcMin/+ mice with spontaneous intestinal adenomas, which bodes well for R-spondin 1 and Slit2 as potential adjuvant therapies to reduce gut toxicity in patients with cancer.
References
Zhou, W.-J. et al. Induction of intestinal stem cells by R-spondin 1 and Slit2 augments chemoradioprotection. Nature 10.1038/nature12416
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Plausible mechanism for chemoradioprotection identified. Nat Rev Clin Oncol 10, 547 (2013). https://doi.org/10.1038/nrclinonc.2013.151
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DOI: https://doi.org/10.1038/nrclinonc.2013.151