Nav: Home

Fat cells may inactivate chemotherapeutic drug

November 08, 2017

Bottom Line: Adipocytes, or fat cells, can absorb and metabolize the chemotherapeutic agent daunorubicin, reducing the effectiveness of the drug and potentially contributing to poorer treatment outcomes.

Journal in Which the Study was Published:Molecular Cancer Research, a journal of the American Association for Cancer Research.

Authors: Steven Mittelman, MD, PhD, associate professor of pediatrics and the division chief of pediatric endocrinology at UCLA Mattel Children's Hospital in Los Angeles.

Background: "Anthracyclines such as daunorubicin are important chemotherapy agents used in a variety of cancers in children and adults, including leukemia," Mittelman said. "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 research has shown that obesity is associated with poorer outcomes from several kinds of cancer, including breast, colon, ovarian, and prostate cancers. Research has suggested that excess adiposity can affect the "pharmacokinetics" of chemotherapy, or the way drugs are absorbed, metabolized, and excreted from the body.

How the Study Was Conducted and Results: Mittelman and colleagues sought to examine how obesity might alter the effectiveness of daunorubicin. They cocultured human acute lymphoblastic leukemia (ALL) cell lines with adipocytes and treated them with daunorubicin. They also studied whether human adipose tissue from cancer patients could metabolize daunorubicin. They measured the presence of daunorubicin through flow cytometry and liquid chromatography/mass spectrometry, and examined fat cells in bone marrow from children with leukemia.

The study's key findings, according to Mittelman, are:
  • The presence of adipocytes significantly reduced the accumulation of daunorubicin in the ALL cells.

  • The adipocytes absorbed the chemotherapeutic agent, removing it from the leukemia microenvironment. The leukemia 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 leukemia cells.


Authors' Comments: "The finding that human fat cells can metabolize and inactivate a chemotherapy is novel and surprising," 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."

Fellow author Etan Orgel, MD, MS, attending physician at Children's Hospital Los Angeles and an assistant professor of clinical pediatrics at the Keck School of Medicine at the University of Southern California, 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 said.

Limitations: Mittelman said the study's primary limitation is that the researchers were unable to measure the exact concentration of daunorubicin in the leukemia cells in patients.
-end-
Funding and Disclosures: This study was performed at The Saban Research Institute at Children's Hospital Los Angeles, and funded by the National Cancer Institute, the Saban Research Institute, the Office of the Dean of the Keck School of Medicine, a Translational Research Program Award from the Leukemia & Lymphoma Society, the V Foundation for Cancer Research, and the National Center for Advancing Translational Science of the National Institutes of Health. The authors declare no conflicts of interest.

Follow us: Cancer Research Catalyst http://blog.aacr.org; Twitter @AACR; and Facebook http://www.facebook.com/aacr.org

About the American Association for Cancer Research

Founded in 1907, the American Association for Cancer Research (AACR) is the world's first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR membership includes more than 37,000 laboratory, translational, and clinical researchers; population scientists; other health care professionals; and patient advocates residing in 108 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis, and treatment of cancer by annually convening more than 30 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 21,900 attendees. In addition, the AACR publishes eight prestigious, peer-reviewed scientific journals and a magazine for cancer survivors, patients, and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the Scientific Partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration, and scientific oversight of team science and individual investigator grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and other policy makers about the value of cancer research and related biomedical science in saving lives from cancer. For more information about the AACR, visit http://www.AACR.org.

American Association for Cancer Research

Related Cancer Articles:

UCI researchers uncover cancer cell vulnerabilities; may lead to better cancer therapies
A new University of California, Irvine-led study reveals a protein responsible for genetic changes resulting in a variety of cancers, may also be the key to more effective, targeted cancer therapy.
Breast cancer treatment costs highest among young women with metastic cancer
In a fight for their lives, young women, age 18-44, spend double the amount of older women to survive metastatic breast cancer, according to a large statewide study by the University of North Carolina at Chapel Hill.
Cancer mortality continues steady decline, driven by progress against lung cancer
The cancer death rate declined by 29% from 1991 to 2017, including a 2.2% drop from 2016 to 2017, the largest single-year drop in cancer mortality ever reported.
Stress in cervical cancer patients associated with higher risk of cancer-specific mortality
Psychological stress was associated with a higher risk of cancer-specific mortality in women diagnosed with cervical cancer.
Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.
Moffitt Cancer Center researchers identify one way T cell function may fail in cancer
Moffitt Cancer Center researchers have discovered a mechanism by which one type of immune cell, CD8+ T cells, can become dysfunctional, impeding its ability to seek and kill cancer cells.
More cancer survivors, fewer cancer specialists point to challenge in meeting care needs
An aging population, a growing number of cancer survivors, and a projected shortage of cancer care providers will result in a challenge in delivering the care for cancer survivors in the United States if systemic changes are not made.
New cancer vaccine platform a potential tool for efficacious targeted cancer therapy
Researchers at the University of Helsinki have discovered a solution in the form of a cancer vaccine platform for improving the efficacy of oncolytic viruses used in cancer treatment.
American Cancer Society outlines blueprint for cancer control in the 21st century
The American Cancer Society is outlining its vision for cancer control in the decades ahead in a series of articles that forms the basis of a national cancer control plan.
Oncotarget: Cancer pioneer employs physics to approach cancer in last research article
In the cover article of Tuesday's issue of Oncotarget, James Frost, MD, PhD, Kenneth Pienta, MD, and the late Donald Coffey, Ph.D., use a theory of physical and biophysical symmetry to derive a new conceptualization of cancer.
More Cancer News and Cancer Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Warped Reality
False information on the internet makes it harder and harder to know what's true, and the consequences have been devastating. This hour, TED speakers explore ideas around technology and deception. Guests include law professor Danielle Citron, journalist Andrew Marantz, and computer scientist Joy Buolamwini.
Now Playing: Science for the People

#576 Science Communication in Creative Places
When you think of science communication, you might think of TED talks or museum talks or video talks, or... people giving lectures. It's a lot of people talking. But there's more to sci comm than that. This week host Bethany Brookshire talks to three people who have looked at science communication in places you might not expect it. We'll speak with Mauna Dasari, a graduate student at Notre Dame, about making mammals into a March Madness match. We'll talk with Sarah Garner, director of the Pathologists Assistant Program at Tulane University School of Medicine, who takes pathology instruction out of...
Now Playing: Radiolab

What If?
There's plenty of speculation about what Donald Trump might do in the wake of the election. Would he dispute the results if he loses? Would he simply refuse to leave office, or even try to use the military to maintain control? Last summer, Rosa Brooks got together a team of experts and political operatives from both sides of the aisle to ask a slightly different question. Rather than arguing about whether he'd do those things, they dug into what exactly would happen if he did. Part war game part choose your own adventure, Rosa's Transition Integrity Project doesn't give us any predictions, and it isn't a referendum on Trump. Instead, it's a deeply illuminating stress test on our laws, our institutions, and on the commitment to democracy written into the constitution. This episode was reported by Bethel Habte, with help from Tracie Hunte, and produced by Bethel Habte. Jeremy Bloom provided original music. Support Radiolab by becoming a member today at Radiolab.org/donate.     You can read The Transition Integrity Project's report here.