A com­mon di­a­betes drug could help treat can­cer, based on its in­sulin, obe­sity links

Lodi News-Sentinel - - LOCAL/NATION - By Marie McCul­lough

Be­ing too fat raises the risk of Type 2 di­a­betes. That’s com­mon knowl­edge.

What is less well-known is that sci­en­tists have linked can­cer to the same obe­sity-re­lated meta­bolic ab­nor­mal­i­ties that drive di­a­betes — es­pe­cially re­sis­tance to in­sulin, the hor­mone that en­ables cells to ab­sorb blood sugar and turn it into en­ergy.

In­deed, an Amer­i­can Can­cer So­ci­ety re­port pub­lished this week shows that while over­all can­cer rates have been fall­ing for 25 years, partly be­cause of less smok­ing, obe­sity-re­lated can­cer deaths are ris­ing.

The bi­o­logic con­nec­tions are com­plex and still un­clear, but they fit with a hall­mark of can­cer that was rec­og­nized a cen­tury ago: Malig­nant cells thrive on sugar, or glu­cose. They take up much more glu­cose than healthy tis­sue.

Obese pa­tients’ high blood sugar “may im­pact tu­mor growth by pro­vid­ing can­cer cells with an abun­dance of fuel,” ex­plains a re­view ar­ti­cle co-au­thored by Ryan Dowl­ing, a bio­chemist at Princess Mar­garet Can­cer Cen­ter in Toronto.

Although the world­wide obe­sity epi­demic makes this can­cer link omi­nous, the evolv­ing un­der­stand­ing of it sug­gests that tar­get­ing in­sulin re­sis­tance could have an­ti­cancer ef­fects. That’s why met­formin, the main­stay di­a­betes drug that re­duces the liver’s re­lease of glu­cose, is be­ing in­ves­ti­gated to help treat and even pre­vent can­cer. Scores of clin­i­cal tri­als around the world are test­ing it in breast, blad­der, lung, colon, gy­ne­co­log­i­cal and other ma­lig­nan­cies.

“I don’t think any­body ex­pects that met­formin will have a dras­tic or long-term ef­fect on can­cer by it­self,” said Fox Chase Can­cer Cen­ter on­col­o­gist Daniel Geynis­man, who is con­duct­ing a trial of met­formin in prostate can­cer that has come back after con­ven­tional treat­ment. “The ques­tion is, can it aug­ment our stan­dards of care — not to men­tion help­ing with” in­sulin re­sis­tance.

Met­formin also has the plus of be­ing a well-tol­er­ated, in­ex­pen­sive, generic drug.

“It costs pen­nies a day,” said Dowl­ing in Toronto. “If it were to work, it would be a mas­sive bonus.”

Start­ing 50 years ago, pop­u­la­tion-based stud­ies found that di­a­betes in­creased the risk of nu­mer­ous types of can­cer, and wors­ened the out­look. But an “as­so­ci­a­tion,” as sci­en­tists call it, just raises a red flag.

“A crit­i­cal ques­tion is whether the asso­ciations be­tween di­a­betes and the risk of cer­tain can­cers is largely due to shared risk fac­tors (obe­sity, poor diet, phys­i­cal in­ac­tiv­ity and aging), or whether ... the meta­bolic de­range­ments typ­i­cal of di­a­betes in­crease the risk for some types of can­cer,” the Amer­i­can Can­cer So­ci­ety and Amer­i­can Di­a­betes As­so­ci­a­tion wrote in a 2010 joint re­port on di­a­betes and can­cer.

Re­searchers are still de­ci­pher­ing the an­swer. Stud­ies in cells and an­i­mals show that sig­nal­ing pro­teins se­creted by fat, called adipokines, are al­tered in obe­sity and some­times over­stim­u­late can­cer cells. Chronic in­flam­ma­tion and sex hor­mones also seem to con­trib­ute to the in­ter­play of obe­sity and can­cer. But in­sulin, pro­duced by the pan­creas to reg­u­late blood sugar, is most con­sis­tently im­pli­cated as a cul­prit in can­cer de­vel­op­ment and out­comes.

Many types of can­cer cells grown in lab dishes, par­tic­u­larly breast can­cer cells, pro­duce an abun­dance of pro­tein “re­cep­tors” that re­ceive sig­nals from in­sulin and a closely re­lated hor­mone called in­sulin­like growth fac­tor. This sig­nal­ing net­work helps malig­nant cells get and use glu­cose, and may ac­ti­vate path­ways that drive can­cer cell growth, pro­lif­er­a­tion, sur­vival, and metas­ta­sis, the deadly spread to dis­tant tis­sues.

“It also ap­pears that in­sulin (sig­nal­ing) may stim­u­late nor­mal cells that are in­volved in can­cer pro­gres­sion,” such as smooth mus­cle cells that form new blood ves­sels needed by tu­mors, said the ADA/ACA joint re­port.

On­go­ing tri­als in less for­mi­da­ble can­cers are ex­pected to re­veal whether met­formin has ben­e­fits — and sur­vival is not the only mea­sure. Some stud­ies are also look­ing at weight loss, meta­bolic fac­tors, car­dio­vas­cu­lar dis­ease, and qual­ity of life.

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