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Monday, September 24, 2012

Optimized tumor treatment through starvation


There’s good news and bad news about brain cancer treatment. The good news is that Fernando Safdie of the University of Southern California and his colleagues may have found a way to boost the effects of chemotherapy and radiotherapy without damaging healthy cells. The bad news is that the method involves starvation.

The most common type of brain cancer is glioma. Treatment usually includes surgery, radiation and chemotherapy, but even with all that the five-year survival rate is less than 3%. The standard chemotherapy drug for this type of cancer is Temozolomide (TMZ) but it can only temporarily halt the growth of brain tumors. Meanwhile, these treatments damage healthy tissue as well as cancerous cells. Obviously, any approach that can improve these odds is worth investigating. 

Why pursue fasting as a treatment? Unlike normal cells, under times of duress, cancer cells don’t transfer scant resources from growth to maintenance functions. Thus, the tumor cells are particularly vulnerable to starvation. The researchers hope that fasting can cause these toxic therapies (chemotherapy and radiotherapy) to preferentially attack tumors rather than healthy tissues.

‘Short-term starvation’ was tested both in vitro, with glioma cell cultures, and in mice. In both cases, tumor cells but not normal cells were sensitized to TMZ. In fact, starvation alone slowed tumor growth as much as chemotherapy alone, though the greatest benefit was seen with fasting and chemotherapy. Mice that fasted and got TMZ had the smallest tumors and survived the longest. The same pattern held for radiotherapy. Mice that had been deprived of food had the best outcomes.

I’d like to point out that each enforced fast lasted 48 hours, and the mice underwent two cycles of fasting during their treatment. In other words, this treatment will have to have an amazing success rate before any humans are willing to try it. That doesn’t seem to be the case yet. Although the fasting mice fared better, all but one eventually succumbed to their tumors. To be fair, the fasting mice did not appear to suffer from their deprivations. Judging by their activity and general interest in their surroundings, they felt better than their non-fasting cohorts, possibly because the chemotherapy was not devastating their healthy tissues to the same extent. 

Safdie F, Brandhorst S, Wei M, Wang W, Lee C, Hwang S, Conti PS, Chen TC, & Longo VD (2012). Fasting enhances the response of glioma to chemo- and radiotherapy. PloS one, 7 (9) PMID: 22984531