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Fat Cells May Hinder Chemotherapy’s Impact

What new research means for patients struggling with obesity

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It’s hardly newsworthy that obesity leads to a litany of health problems, from heart disease and high blood pressure to diabetes, sleep apnea and cancer. But for cancer patients, a new study suggests obesity may cause even more medical complications by interfering with efforts to treat the disease. Citing the results of research published in Molecular Cancer Research, a National Cancer Institute report details how fat cells may reduce the potency of chemotherapy drugs. “Researchers have shown that fat cells can absorb two commonly used chemotherapy drugs and break them down chemically into less toxic forms, potentially reducing the drugs’ effectiveness” on certain cancers, the NCI staff says in a recent blog on the study.

“By absorbing and breaking down the drugs, the fat cells may be removing the drugs from the immediate environment around tumor cells in bone marrow or other areas of the body where fat cells are plentiful,” according to the study. “This finding may help explain why obesity is linked to poorer outcomes in several types of cancer.” The study’s lead investigator noted that the research appears to be the first to offer evidence that fat cells may “metabolize and inactivate any therapeutic drug.”

Doctors had previously observed that obese children with acute lymphoblastic leukemia were 50 percent more likely to have a recurrence than their non-obese counterparts. Obese patients with breast, colon, ovarian and prostate cancers have also seen poorer outcomes than those who are not obese. Damien Hansra, MD, Medical Oncologist at Cancer Treatment Centers of America© in Newnan, Georgia, explains that chemotherapy drugs work by impairing cancer cells’ ability to divide so that tumors cannot grow and spread. But researchers are finding that obesity complicates the drugs’ impact by altering the tumor microenvironment, or the cells, molecules and blood vessels that surround and feed a tumor cell. This process creates a biological environment in obese patients that may cause tumors to grow.

Impact of inflammation

Obesity leads to increased inflammation, which has been linked to a variety of cancers. A University of Miami study published in 2017 found that “obesity is associated both with a higher risk of developing breast cancer, particularly in postmenopausal women, and with worse disease outcome for women of all ages.”

Overweight and obese people are more likely to have medical conditions that cause chronic inflammation, increasing their risk of certain cancers. In the leukemia study, investigators found that fat cells, which produce high levels of certain enzymes, may break down a class of chemotherapy drugs known as anthracyclines. Some of these enzymes were found in the fat cells of bone marrow in children being treated for acute lymphoblastic leukemia. Absorbing or breaking down the concentration of certain cancer drugs may contribute to “the emergence of drug-resistant tumor cells,” according to the study.

Over the years, under-dosing obese cancer patients, because of concern about cardiotoxicity (damage to the heart caused by the chemotherapy drugs), has stirred controversy, Dr. Hansra says. But in 2012, the American Society of Clinical Oncology, after studying the issue, recommended that “full weight-based cytotoxic chemotherapy doses be used to treat obese patients with cancer, particularly when the goal of treatment is cure. There is no evidence that short or long-term toxicity is increased among obese patients receiving full weight-based doses.”

Dr. Hansra is passionate about educating his patients about the serious health risks obesity poses. “Obesity is a systemic, preventable, multi-system inflammatory disease,” he says.

“It’s a definite marker of inferior health,” he says. “Key obesity-related syndromes are cardiovascular disease, cerebrovascular “diseases (affecting the brain and its blood vessels and arteries), diabetes, high cholesterol, hypertension, kidney disorders and musculoskeletal disorders, all of which require people to take more medications. Add in chemotherapyhormone therapy and/or radiation therapy for a patient who’s already sick, and it’s a storm of illness, and you’re going to see more and more adverse drug interactions.”

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