A new report published in Molecular Cancer Research showed that adipocytes (fat cells) can absorb and metabolize the chemotherapeutic agent daunorubicin and thus decrease its efficiency and potentially be contributing to poorer treatment outcomes.
Dr Steven Mittelman, associate professor of paediatrics said, "Anthracyclines such as daunorubicin are important chemotherapy agents used in a variety of cancers in children and adults, including leukaemia.
It is necessary to better understand how some leukaemia cells are able to avoid and resist this and other chemotherapies, so the better strategies to improve the treatment outcomes can be developed.
Previous research has shown that obesity is associated with poorer outcomes from several kinds of cancer. Research has suggested that excess adiposity can affect the pharmacokinetics of chemotherapy, or the way drugs are absorbed, metabolized, and excreted from the body.
The researchers wanted to examine how obesity might alter the effectiveness of daunorubicin. They cocultured human acute lymphoblastic leukaemia (ALL) cell lines with adipocytes and treated them with daunorubicin.
The team also studied whether human adipose tissue from cancer patients could metabolize daunorubicin. The researchers measured the presence of daunorubicin through flow cytometry and liquid chromatography/mass spectrometry and examined fat cells in bone marrow from children with leukaemia.
The presence of adipocytes significantly reduced the accumulation of daunorubicin in the ALL cells. The cells absorbed the chemotherapeutic agent, removing it from the leukaemia microenvironment. The leukaemia cells treated with daunorubicin survived and proliferated better in samples that contained adipocytes.
The adipocytes metabolized daunorubicin. Enzymes in the fat cells changed the structure of the chemotherapy molecule, making it much less toxic to the leukaemia cells. The finding that human fat cells can metabolize and inactivate chemotherapy is novel and surprising," Mittelman said.
He added that this is important for leukaemia and a lot of other cancers that grow in the bone marrow or around fat cells since that means that fat cells might remove chemotherapy from the environment and allow the cancer cells to survive.
Fellow author Dr Etan Orgel said the study's findings indicate a need for further research to determine whether adipocytes have a similar effect on other types of chemotherapy and if a similar effect occurs in other types of cancer.A deeper understanding of the process could lead clinicians to deliver more effective treatment by choosing or designing chemotherapy drugs that are more resistant to the enzymes in fat cells, he added.