‘Bar-cod­ing’ sys­tem used in brain can­cer re­search

Winnipeg Free Press - - NEWS - SH­ERYL UBELACKER

TORONTO — A Cana­dian-led in­ter­na­tional re­search team is us­ing a “bar-cod­ing” sys­tem to in­ves­ti­gate the growth pat­terns of in­di­vid­ual cells that make up the dead­li­est form of brain can­cer, with the hopes of im­prov­ing treat­ment.

Known as glioblas­toma, it’s con­sid­ered among the “nas­ti­est” of hu­man can­cers and is the kind of brain tu­mour di­ag­nosed last year in Trag­i­cally Hip front­man Gord Downie.

Each year in Canada, about 1,500 adults and 150 chil­dren are di­ag­nosed with glioblas­toma, an ag­gres­sive tu­mour that is no­to­ri­ous for its com­plex ge­netic makeup and poor re­sponse to treat­ment. Glioblas­toma has an av­er­age five-year sur­vival rate of only about 10 per cent, and most peo­ple suc­cumb to the dis­ease within roughly 15 months of di­ag­no­sis.

But re­search led by the Hos­pi­tal for Sick Chil­dren in Toronto and the Univer­sity of Cam­bridge in the United King­dom is tak­ing a novel ap­proach to bet­ter un­der­stand­ing how in­di­vid­ual cells in the tu­mour con­trib­ute to its growth and what types of drugs might best tar­get this highly in­va­sive brain can­cer.

“What we did here was we took hu­man tu­mours, broke them up into in­di­vid­ual cells and then we in­fected those with a short DNA se­quence,” said co­prin­ci­pal in­ves­ti­ga­tor Dr. Peter Dirks, a neu­ro­sur­geon and re­searcher at the Hos­pi­tal for Sick Chil­dren.

In the lab, ev­ery cell was tagged with a dif­fer­ent DNA bar code, giv­ing them a unique iden­ti­fy­ing marker, he said.

“So now we have thou­sands of bar codes in thou­sands of dif­fer­ent cells.

“That gets in­te­grated into the DNA of that cell, and as that cell di­vides, all the daugh­ter cells of that la­belled cell share the same bar code. It’s a very pow­er­ful way of just trac­ing the po­ten­tial of each cell in the tu­mour.”

These hu­man glioblas­toma cells were then put into the brains of spe­cially bred lab mice and al­lowed to con­tinue di­vid­ing to form tu­mours. When the tu­mours were re­moved, DNA from each cell was se­quenced and their bar codes iden­ti­fied.

“What that se­quenc­ing was able to do was tell us what are the bar codes that are there and what are the fre­quency of the bar codes,” Dirks said. “So it’s telling us, did ev­ery cell go on and form a tu­mour or did only some of the bar codes get seen in the tu­mour later.”

Us­ing this cell-track­ing strat­egy, the re­searchers found that only a small pro­por­tion of the bar-coded cells could give rise to long-term tu­mour growth, sug­gest­ing that a large pro­por­tion of pa­tient tu­mours con­tain cells that can­not mul­ti­ply to make tu­mours grow.

They found that glioblas­toma is made up of many dif­fer­ent clones — mini­cancers com­prised of clumps of ge­net­i­cally iden­ti­cal cells within the tu­mour — and most fol­lowed a growth pat­tern con­sis­tent with the stem cell model of can­cer, in which a mi­nor­ity of stem cells are re­spon­si­ble for tu­mour growth.

Mini-can­cers that fol­lowed this pre­dictable growth pat­tern were dubbed Group A, while rarer and more ag­gres­sive clones that didn’t were la­belled Group B.

“Con­sider it like a marathon race, where all the com­peti­tors are to­gether in the race,” Dirks said. “The whole pack tends to move along, but there are some sprint­ers that go way be­yond the pack.

“So we think there are some of those that are like rogue clones that re­ally are burst­ing ahead of the oth­ers — those are the Bs.”

What’s key about these find­ings, pub­lished Wed­nes­day in the jour­nal Na­ture, is they sug­gest a dif­fer­ent way of tar­get­ing the brain tu­mour.

The re­searchers have iden­ti­fied two ex­ist­ing can­cer drugs that were shown to slow the pro­lif­er­a­tion of glioblas­toma cells in lab mice, one that acts on Group A cells and the other against Group B.

“It’s about pro­mot­ing dif­fer­ent types of ther­a­pies for can­cer,” Dirks said. “It’s another step in can­cer treat­ment, not tar­get­ing the one mu­ta­tion but tar­get­ing the pro­cesses that fa­cil­i­tate the stem cell be­hav­iour of can­cer cells.”

Dirks cau­tioned, how­ever, that there’s still much more re­search needed be­fore it’s known whether these find­ings could lead to an ef­fec­tive ther­apy for pa­tients with the dev­as­tat­ing brain tu­mour.

“I don’t feel as dis­il­lu­sioned as I used to,” he said. “These kind of stud­ies are still a ways away from the clinic, but it’s given me new op­ti­mism.”

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