A new study published in the recent issue of the journal Molecular Cancer Research revealed that adipocytes or fat cells could absorb and metabolize the chemotherapeutic drug daunorubicin, resulting in the reduced efficacy of the drug, ultimately leads to the worst treatment outcomes.
Daunorubicin is an anthracycline anti-tumor drug used in the variety of cancers in children and adults, including leukemia. There is a need to better understand how some leukemia cells are able to avoid and resist daunorubicin and other chemotherapies to can develop better strategies to improve treatment outcomes.
Studies have demonstrated that obesity contributes to poorer treatment outcomes in some cancer types, including colon, breast, ovarian, and prostate cancers. The current research suggests that excess adiposity could affect the pharmacokinetic factors like absorption, metabolism, and excretion, of chemotherapeutic drugs.
In order to study the impact of obesity on daunorubicin efficacy, the research team led by Steven Mittelman at UCLA Mattel Children's Hospital in Los Angeles cocultured human acute lymphoblastic leukemia (ALL) cell lines with adipocytes and examined the interaction of daunorubicin with the coculture.
Additionally, they have examined whether human adipose tissue derived from cancer patients could metabolize daunorubicin. They measured the presence of daunorubicin using flow cytometry and liquid chromatography/mass spectrometry and analyzed fat cells in bone marrow from children with leukemia.
The researchers found that presence of adipocytes has a negative impact on the daunorubicin accumulation in the ALL cells. The adipocytes cells removed daunorubicin from the leukemia microenvironment and absorbed it. Daunorubicin treated leukemia cells showed higher survival rate and proliferated better in the presence of adipocytes. With the help of enzymes, the adipocytes metabolized daunorubicin by transforming it to less toxic for the leukemia cells.
The current study is the first and surprising to find that human fat cells could metabolize and inactivate a chemotherapy, said the corresponding author Mittelman. "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 study findings show that further studies are required to evaluate the possible analogous effect of adipocytes on other types of chemotherapy and even in other forms of cancer, noted Etan Orgel, an assistant professor of clinical pediatrics at the Keck School of Medicine at the University of Southern California.
A better insight into the drug metabolism could help guide clinicians to provide more effective therapy for the patient by identifying the chemotherapeutic agent that exhibits more resistance to the enzyme in fat cells, Orgel concluded.