Understanding why metastatic breast cancer is so difficult to treat

Michael Wendt. Photo by Vincent Walter

04/22/2016 |

Michael Wendt was on a trajectory toward medical school, studying biology in a small liberal arts college along the banks of a meandering river and staying up late to prepare for his Medical College Admission Test (MCAT) entrance exams, when a rotation in a local emergency room stopped him in his tracks.

“I liked working with the patients, but the work itself just wasn’t that interesting,” says Wendt, who realized that his previous stint in a laboratory at the Medical College of Wisconsin, spending long hours studying cell cultures in petri dishes, had been far more appealing. “What interested me more was the science behind the care — what you could do to lead to a product or a drug that could immediately affect a person’s health.”

So Wendt switched career paths, ultimately landing at Case Western Reserve University in urban Cleveland, where he studied the phenomenon of epithelial-mesenchymal transition (EMT), a process researchers are now learning makes metastatic breast cancer more difficult to treat.

When tumors are removed from the breast, any stray cells that have migrated away from the original tumor site metastasize and become resistant to currently available therapies. That’s because of EMT, which causes them to change characteristics as they leave the breast.

“The primary tumor you are getting the diagnosis from is not what you’re trying to treat,” says Wendt, an assistant professor of medicinal chemistry and molecular pharmacology. “That is removed via lumpectomy. These metastases are really, really different, and clinically that correlates with the failure of a lot of therapies.”

So Wendt is studying exactly when and how spreading tumors change and become resistant to available treatments. Establishing cell lines that have undergone EMT and acquired resistance to currently available medications, he’s discovered several potential targets that may be responsible for the EMT process and resistance.

“The goal of our lab is to understand the plasticity of tumor cells and get to the heart of that,” Wendt says. “Breast cancer is a great example of the potential of personalized medicine; the clinical oncologist has a big bag of drugs that can target very specific growth factor pathways, but once those fail, women are limited to general toxic chemotherapy. The future of personalized medicine lies in the appropriate application of therapeutics that target very specific aspects of cancer cell biology.”

– Angie Roberts
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