Why treatment outcome is worse in obese cancer patients

Examining why obese patients fare worse than leaner patients across many cancer types, a new study has found that cancer stem cells not only use fatty tissue as a robbers' cave to hide from therapy, but actively adapt this cave to their liking.

Leukemia stem cells "hide" in fatty tissue, even transforming this tissue in ways that support their survival when challenged with chemotherapy, the study found.

"It's been increasingly appreciated that cancer can originate in stem cells and that failing to kill cancer stem cells can lead to relapse,” said Craig Jordan, Professor at University of Colorado Anschutz Medical Campus in the US.

The group started by examining cancer cells found in the adipose tissue of a mouse model of leukemia. Rather than the expected mix of regular cancer cells with cancer stem cells, the group found that this fatty tissue was enriched for cancer stem cells.

The researchers found that it was the cancer stem cells that exploited the robbers' cave of fatty tissue. These stem cells in fatty tissue powered their survival and growth with fatty acids, manufacturing energy by the process of fatty acid oxidisation.

In fact, these adipose tissue stem cells actively signal fat to undergo a process called lipolysis which releases fatty acids into the microenvironment.
"The basic biology was fascinating: the tumour adapted the local environment to suit itself," Jordan said.

Finally, when the group challenged these cells with chemotherapy they discovered that stem cells in fatty tissue that had switched their energy source to fatty acids were more resistant than stem cells outside this tissue.

When the researchers examined samples of human leukemia, they found characteristics similar to the mouse models cells specialised to use fatty acids as their energy source were more resistant to chemotherapy.

The study was published in the journal Cell Stem Cell. If further work bears out this hypothesis, it could help to explain the fact of poorer outcomes in obese patients, the researchers said.