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April 29, 2009

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Anthrax may be ally in cancer war

Dec. 29, 2007
Courtesy American Society for 
Biochemistry and Molecular Biology
and World Science staff

Most peo­ple would­n’t con­sid­er an­thrax tox­in to be help­ful—but this bac­te­ri­al poi­son may some­day be a can­cer ther­a­py, sci­en­tists claim. 

The tox­in has been shown to be fairly se­lec­tive in tar­get­ing mel­a­no­ma, or skin can­cer, cells, ac­cord­ing to Ste­phen Lep­pla of the Na­t­ional In­sti­tute of Al­ler­gy and In­fec­tious Dis­eases in Be­thes­da, Md.

In a new stu­dy, Lep­pla and col­leagues mod­i­fied the tox­in to make it tar­get tu­mor cells even more pre­cise­ly, while spar­ing healthy cells. To work, the re­search­ers said, the new poi­son re­quires the pres­ence of pro­teins over­pro­duced only in can­cer cells. The pro­teins are called ma­trix met­al­lo­pro­tein­ases.

The team found that all mice tested with the mu­tat­ed tox­in tol­er­ated doses that would be oth­er­wise le­thal. The mu­tat­ed poi­son was al­so bet­ter at kill­ing mel­a­no­ma tu­mors than nat­u­ral tox­in, they said, due to its high­er spe­cif­i­city and long­er pres­ence in the blood.

Even bet­ter, Lep­pla and col­leagues said, the molecule’s an­ti-can­cer ac­ti­vity was­n’t lim­it­ed to mel­a­no­ma: the poi­son could al­so kill oth­er tu­mors like co­lon and lung. This abil­ity was due, they re­ported, to its power to in­hib­it an­gio­gen­esis, or the forma­t­ion of new blood ves­sels that nour­ish tu­mors.

“These en­cour­ag­ing mouse re­sults sug­gest that mod­i­fied an­thrax tox­in could be clin­ic­ally vi­a­ble, and this po­tent kill­er might some­day be put to good use,” said an an­nounce­ment of the find­ings this week from the Ame­ri­can So­ciety for Bio­chem­is­try and Mo­l­e­cu­lar Bio­logy. The org­a­ni­za­tion pub­lishes the Jour­nal of Bi­o­log­i­cal Chem­is­try, which reports the new study in its Jan. 4 is­sue.

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Most people wouldn’t consider anthrax toxin to be helpful—but this bacterial poison may someday be a good cancer therapy, scientists claim. The toxin has been shown to be fairly selective in targeting melanoma, or skin cancer, cells, according to Stephen Leppla of the National Institute of Allergy and Infectious Diseases in Bethesda, Md. In a new study, Leppla and colleagues modified the toxin to make it target tumor cells even more precisely, while sparing healthy cells. To work, the researchers said, the new poison requires the presence of proteins that are overproduced only in cancer cells, called matrix metalloproteinases. The team found that all mice tested with the mutated toxin tolerated doses that would be otherwise lethal. The mutated poison was also better at killing melanoma tumors than natural toxin, they said, due to its higher specificity and longer presence in the blood. Even better, Leppla and colleagues said, the molecule’s anti-cancer activity wasn’t limited to melanoma: the poison could also kill other tumors like colon and lung. This widespread effectiveness, they reported, was due to the toxin’s ability to inhibit angiogenesis, or the formation of new blood vessels that nourish tumors. The “encouraging mouse results suggest that modified anthrax toxin could be clinically viable, and this potent killer might someday be put to good use,” the researchers said in an announcement of their findings this week. The study appears in the Jan. 4 issue of the Journal of Biological Chemistry.