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New anti-cancer strategy: make tumor cells age

March 17, 2010
Courtesy of Nature Publishing Group
and World Science staff

Re­search­ers have identified a chem­i­cal chain of events that leads can­cer cells to age, and thus stop re­pro­duc­ing. By exp­loit­ing this process, they pro­pose, sci­en­tists might be able to de­vel­op new can­cer ther­a­pies.

The mo­lec­u­lar se­quence of events, called a sig­nal­ing path­way, is de­scribed in the March 18 is­sue of the research jour­nal Na­ture by in­ves­ti­ga­tors Pa­o­lo Pan­dolfi of the Har­vard Med­i­cal School and col­leagues.

Can­cer cells are nor­mally able to re­pro­duce them­selves in­def­i­nitely with­out age­ing; this in­deed is a co­re as­pect of the prob­lem con­fronting can­cer vic­tims. The out-of-control cell di­vi­sion leads to the crea­t­ion of an ever-growing load of tu­mors.

The newfound pathway drives cell ag­ing, or “se­nes­cence,” only in can­cerous con­di­tions, according to Pan­dol­fi’s group. A key com­po­nent of the path­way is a gene called Skp2, the sci­en­tists re­ported. By sup­press­ing this gene, they found that they could pro­foundly re­strict tu­mor forma­t­ion in mice by caus­ing can­cer cells to age. The pro­cess curbed cell di­vi­sion.

The re­search­ers al­so found that a Skp2-blocking drug in­duced ag­ing in a lab­o­r­a­to­ry cul­ture of hu­man pros­tate can­cer cells.

Be­cause the new­found ag­ing path­way seems to op­er­ate only in can­cer, it raises hopes that it could prove a use­ful tar­get for an­ti-can­cer treat­ments, which might avoid harm­ing healthy cells, the re­search­ers ar­gued. Such a treat­ment might al­so have the ad­van­tage of op­er­at­ing in a wide ar­ray of dif­fer­ent can­cer types.

“The chal­lenge ahead is to test wheth­er these pre­clin­i­cal stud­ies in mice can be trans­lated in­to more ef­fec­tive can­cer ther­a­pies,” wrote Man­u­el Ser­rano is of the Span­ish Na­tional Can­cer Re­search Cen­tre in Ma­drid, in a com­men­tary ac­com­pa­nying the study in Na­ture.

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Researchers have discovered a chemical chain of events that leads cancer cells to age, which they argue could aid in the development of a general approach for cancer therapy. The molecular sequence of events, called a signaling pathway, is described in the March 18 issue of the reearch journal Nature by investigators Paolo Pandolfi of the Harvard Medical School and colleagues. Cancer cells are normally able to reproduce themselves indefinitely without ageing; this indeed is a core aspect of the problem confronting cancer victims. The out-of-control cell division leads to the creation of an ever-growing load of tumors. Pandolfi and colleagues identified a new pathway that drives cell aging, or “senescence,” only in cancerous conditions. A key component of the pathway is a gene called Skp2, the scientists reported. By suppressing this gene, the group found that they could profoundly restrict tumor formation in mice by causing cancer cells to age. The process curbed cell division. The researchers also found that a Skp2-blocking drug induced aging in a laboratory culture of human prostate cancer cells. Because the newfound aging pathway seems to operate only in cancer, it raises hopes that it could prove a useful target for anti-cancer treatments, which might avoid harming healthy cells, the researchers argued. Such a treatment might also have the advantage of operating in a wide array of different cancer types. “The challenge ahead is to test whether these preclinical studies in mice can be translated into more effective cancer therapies,” wrote Manuel Serrano is of the Spanish National Cancer Research Centre in Madrid in a commentary accompanying the study in Nature.