UTHealth investigators exploring the link between obesity and cancer from the left are Chieh Tseng, Ph.D.; Mikhail Kolonin, Ph.D.; Tao Zhang, Ph.D.; Fernando Florez; Ali Dadbin; and Alexes C Daquinag, Ph.D.
UTHealth investigators exploring the link between obesity and cancer from the left are Chieh Tseng, Ph.D.; Mikhail Kolonin, Ph.D.; Tao Zhang, Ph.D.; Fernando Florez; Ali Dadbin; and Alexes C Daquinag, Ph.D.

Because obesity promotes the progression of certain cancers, it stands to reason that an obesity treatment might work against tumors as well. To find out, scientists tested an investigational obesity drug in animal models of cancer with promising results.

Tumor growth was suppressed in mice treated with an obesity drug that destroys stem cells from fat tissue known as adipose stromal cells (ASC) in a study led by Mikhail Kolonin, Ph.D., senior author and director of the Center for Metabolic and Degenerative Diseases at the Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases.

“We propose that drugs targeting ASC can be developed as a combination therapy complementing conventional cancer treatments,” wrote Kolonin and his colleagues in a paper that appeared in an issue of Molecular Therapy, a Nature Publishing Group journal.

Kolonin’s team used a drug prototype called D-WAT that had previously been shown to prevent obesity development in animal models. “It works by hunting and killing adipose stromal cells,” he said.

In the current cancer study, D-WAT attacked the microenvironment nourishing the cancer cells. “This resulted in cell death, hemorrhaging and suppressed tumor growth,” Kolonin said. “Cancer cell growth relies on the microenvironment and tumors use ASC to fortify their pipeline of blood vessels. Without the ASC support, tumors are compromised.”

In the United States, more than a third of adults are obese and this year an estimated 1,658,370 million new cases of cancer will be diagnosed, according to reports by the Centers for Disease Control and Prevention and the National Cancer Institute, respectively.

Kolonin’s team was among the first to establish that tumors emits signals that attract ASC from fat tissue. ASC in tumors support the vasculature, suppress anti-tumor immune response, and promote cancer cell survival.

Kolonin’s UTHealth co-authors include first author Alexes Daquinag, Ph.D.; Chieh Tseng, Ph.D.; Yan Zhang, M.D., Ph.D.; Tao Zhang, Ph.D.; and Ali Dadbin.

The study was titled “Targeted Proapoptopic Peptides Depleting Adipose Stromal Cells Inhibit Tumor Growth” and was supported by the Cancer Prevention & Research Institute of Texas (RP100400).

Kolonin is the Harry E. Bovay, Jr. Distinguished University Chair in Metabolic Disease Research. He is also on the faculty of The University of Texas Graduate School of Biomedical Sciences at Houston.