Cancer's Hiding Spots Revealed

Scientists have discovered that a small number of cancer cells manage to escape chemotherapy by hiding out in the thymus, an organ where immune cells mature.

In a new study of mice with lymphoma, MIT biologists have discovered that within thymus, the cancer cells are bathed in growth factors that protect them from the drugs' effects.

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Those cells are likely the source of relapsed tumours, said Michael Hemann, lead author of the study.

"Successful cancer therapy needs to involve a component that kills tumour cells as well as a component that blocks pro-survival signals," said Hemann.

In the new study, the researchers treated mice with lymphoma with doxorubicin, a drug commonly used to treat a wide range of cancers, including blood cancers.

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They found that during treatment, cells that line the blood vessels release cytokines - small proteins that influence immune responses and cell development.

The exact mechanism is not known, but the researchers believe that chemotherapy-induced DNA damage provokes those blood-vessel cells to launch a stress response that is normally intended to protect progenitor cells - immature cells that can become different types of blood cells.

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That stress response includes the release of cytokines such as interleukin-6, which promotes cell survival.

"In response to environmental stress, the hardwired response is to protect privileged cells in that area, i.e., progenitor cells. These pathways are being coopted by tumour cells, in response to the frontline cancer therapies that we use," said Hemann.

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The discovery marks the first time scientists have seen a protective signal evoked by chemotherapy in the area surrounding the tumour, known as the tumour microenvironment.

"It's completely unexpected that drugs would promote a survival response. The impact of local survival factors is generally not considered when administering chemotherapy, let alone the idea that frontline chemotherapy would induce pro-survival signals," he said.

It remains to be seen if the results will translate to human patients, but the finding does suggest several potential drug targets, including IL-6 and a protein called Bcl2, which is activated by IL-6 and signals cells to stay alive.

This finding could also help explain why tumours that have spread to other parts of the body before detection are more resistant to frontline chemotherapy.

The findings were published in the journal Cell.

Source-ANI