July 31, 2013

expert reaction to intestinal cell protection and chemotherapy in mice

A study published in Nature has suggested that treating intestinal stem cells with certain substances may enhance tolerance to aggressive chemoradiotherapy in mice.

Professor Janusz Jankowski, Sir James Black Professor of Medicine and Associate Dean of Research, Plymouth University, said:

 “This is a timely manuscript as it addresses the issues pertinent to clinical medicine and invasive therapies. In essence doctors are good at knowing whether drugs work (benefit) but we often don’t know in whom these drugs will cause sides effects (risks). This benefit/risk ratio is the pivotal goal of ‘personalised medicine’. In cancer therapy the divide between the benefit and risk elements is particularly precipitous in the form of chemoradiation. The current work shows that by adding to the normal process of stem cell repair (which happens in all animal guts) through treatment with these substances (R-spondin 1 and Slit 2) during chemoradiation therapy, the treated mice have improved resistance to the damage of normal tissue resulting from chemoradiation.

 “There are caveats to this in that animal models were used which may or may not be representative. In addition the dose of radiation given to these mice may be purposefully higher than would be the equivalent to that given in humans, in order to cause stem cell damage and ultimately damage to the whole animal, so the researchers could find the threshold at which damage is irreversible in mice.

 “This manuscript is a proof of principle that we can alter the balance between benefit and risk of therapy, increasing the body’s repair and ultimately the host’s survival. It needs many years of clinical studies to explore the feasibility of extending this work into clinical practice. In the short term there is the hope that gastrointestinal side effects of chemoradiation could be mitigated by novel therapies.”

Professor Owen Sansom, Deputy Director of Cancer Research UK’s Beatson Institute, said:

 “This research in mice is an intriguing discovery. The toxic effects of chemo- and radiotherapy on a cancer patient’s digestive system is one of the main reasons we can’t give higher, more effective doses, and researchers have long sought to find ways to protect a patient’s gut tissue to allow a greater chance of a cure. But this research was only carried out in mice, and – crucially – didn’t show whether the method used would have any effects on cancer cells, which are also thought to be driven by stem cells. So, while these findings are a useful blueprint for how we could focus future effort to protect cancer patients’ digestive systems, this exciting prospect is still a way off yet.”

 ‘Induction of intestinal stem cells by R-spondin 1 and Slit2 augments chemoradioprotection’ by Wei-Jie Zhou et al. was published in Nature.