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Major cancer breakthrough by Toronto scientists: Cancer cells are dormant during chemotherapy

John Dick and his team have discovered that cells are dormant during chemotherapy. (utoronto.ca)John Dick and his team have discovered that cells are dormant during chemotherapy. (utoronto.ca)A team of Toronto cancer researchers have made a breakthrough they say will change the way cancer is studied and even treated.

The team, led by stem cell scientist John Dick of The Princess Margaret Cancer Centre, have discovered that some cancer cells are able to hide from chemotherapy because they are "dormant", only to reactivate at a later time after chemo to cause a recurrence of the disease.

Dick suggests future treatments might involve targeting these dormant cells to become active before chemotherapy, so that they cannot hide from the treatment. One possibility is that changing the location of these cells could activate them and make them susceptible to chemotherapy.

"I suspect that their dormancy also has to do with the environment they are in," says Dick.

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He explains that within a tumour, there are a wide range of cells, including ones that are not cancerous, like blood vessels that provide oxygen and allow for cell growth. It's possible that cancer cells that are not near these types of life-sustaining cells may become dormant, and by moving them, they will become active.

All of these ideas are sure to be the subjects of future investigation.

Perhaps the most surprising finding for Dick and his team is that these dormant cells are genetically identical to the cells that had caused the original cancer.

"These cells share the same genetics, but vary widely in chemotherapy resistance," says Dick. "We stumbled onto something that is a paradox shift in the field."

It represents a shift because while most previous cancer research has focused on identifying genetic mutations and creating drugs to target them, this research suggests  there are other major factors at play, like biology and cell behaviour.

Most people are aware that cancer occurs when genetic mutations cause cells to multiply in an out-of-control fashion. Within a tumour, there are a wide variety of cancerous cells with different mutations that have evolved over the life of the tumour.

"It's like a family tree, with the cells diverging," says Dick.

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In this study, published Thursday in the journal Science, Dick and his team tracked individual human colon cancer cells in mice. They found that some cells kept growing for  up to 500 days, some for a few hundred days, some for less than 100 days, and that some were completely dormant. Importantly, all of these cells, despite their different behaviours, shared the same genetics.

The team expected to find that the longest growing cells would be the ones most frequently responsible for cancer recurrence, but discovered instead that the longest growing cells are generally destroyed by chemotherapy. And rather, it is the dormant cells that are resistant to chemotherapy, which later activate to cause a reoccurance of the disease.

"This study has set us on firm footing," says Dick. "Genetic sequencing is extremely important in cancer research, but this has shown that we can't put all our eggs in one basket. We should be also be looking at the biology and growth properties of cells." 

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