JOIN USIn a study of mice, biologists at the Massachusetts Institute of Technology (MIT) in Cambridge found that a few cancer cells hide inside the thymus -- an organ where immune cells mature -- and escape the treatment.
While hiding there, they are bathed in growth factors that protect them from the drugs' effects. Those cells are likely the source of relapsed tumours, said Michael Hemann, MIT assistant professor of biology, who led the study.
The researchers plan to soon begin tests, in mice, of drugs that interfere with one of those protective factors. Those drugs were originally developed to treat arthritis, and are now in clinical trials for that use.
According to the scientists, such a drug, when used in combination with traditional chemotherapy, can offer a one-two punch to eliminate residual cells and prevent cancer relapse.
"Successful cancer therapy needs to involve a component that kills tumour cells as well as a component that blocks pro-survival signals," said Hemann. "Current cancer therapies fail to target this survival response."
In the new study, published in the journal Cell, the researchers treated mice with lymphoma with doxorubicin, a drug commonly used to treat a wide range of cancers, including blood cancers.
They found that during treatment, cells that line the blood vessels release cytokines -- 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.
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, that is progenitor cells," said Hemann. "These pathways are being coopted by tumor cells, in response to the frontline cancer therapies that we use."
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," said Hemann.
"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."
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.
While the MIT researchers observed this protective effect only in the thymus, they believe there may be other protected areas where tumour cells hide, such as the bone marrow.
This finding could help explain why tumours that have spread to other parts of the body before detection are more resistant to frontline chemotherapy, they added.