Fat Cells Affect Chemotherapy Efficacy

Many factors can impact the efficacy of cancer treatments, including genetics, previous therapies, and type of disease. A new study published by Molecular Cancer Research suggests that weight may also be an important consideration for chemotherapy.

The study authors found that adipocytes may absorb or metabolize daunorubicin chemotherapy, which could impact its efficacy and lead to poor outcomes.

"Anthracyclines such as daunorubicin are important chemotherapy agents used in a variety of cancers in children and adults, including leukemia," said researcher Steven Mittelman, MD, PhD. "We need to better understand how some leukemia cells are able to avoid and resist this and other chemotherapies, so we can develop better strategies to improve our treatment outcomes."

Previous studies have shown that patients with obesity have poor outcomes related to breast, colon, ovarian, and prostate cancers. Researchers have hypothesized that excess fat may affect the way in which chemotherapy works.

In the current study, authors aimed to determine how obesity may impact the efficacy of chemotherapy.

The researchers cultured acute lymphoblastic leukemia (ALL) cells with adipocytes and administered daunorubicin to the cells. They also examined whether human adipose tissue could metabolize the drug.

The authors used flow cytometry and liquid chromatography/mass spectrometry to examine fat cells in the bone marrow of pediatric patients with leukemia.

They discovered that adipocytes significantly reduced the aggregation of chemotherapy in the leukemia cells.

The authors also found that adipocytes absorbed daunorubicin and removed it from the tumor’s microenvironment. Chemotherapy-treated ALL cells had a higher rate of survival and proliferation in samples with the fat cells, according to the study.

Adipocytes were observed to also metabolize chemotherapy. Enzymes in the fat cells altered the structure of daunorubicin and made it less toxic to the cancer cells, according to the study.

These findings suggest that adipocytes can absorb and metabolize daunorubicin, meaning that the drug may not be as effective in patients with obesity compared with normal weight patients, according to the authors.

"The finding that human fat cells can metabolize and inactivate a chemotherapy is novel and surprising," Dr Mittelman said. "This is important for leukemia 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."

The authors said these findings call for additional studies to determine whether this effect is the same for other chemotherapies or other cancers.

"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," said study author Etan Orgel, MD, MS.