Novel Biomarkers Could Help Detect Metastatic Breast Cancer

A human tumor is a complex tissue composed of malignant and non-cancerous tumor-associated cells. Among them are tumor-associated stromal cells, or cells of the tumor microenvironment, which are made up of various types of cells — fibroblasts, endothelial cells, immune cells, adipocytes and others. There is substantial evidence highlighting the contributing role of all these stromal cell types to tumor progression and metastasis.

In a recent study published in Cancer Research, Dorraya El-Ashry, Ph.D., breast cancer researcher at Sylvester Comprehensive Cancer Center, and collaborators studied cancer-associated fibroblasts (CAFs) in the tumor microenvironment. Fibroblasts are cells in the connective tissue that produce collagen and other fibers. Previous studies have found that CAFs facilitate cancer metastasis, even though the exact mechanisms have yet to be elucidated.

“We are currently determining if the presence of these circulating CAFs in the blood of breast cancer patients at high risk for metastases — but without overt metastases yet — can be predictive of metastases and thus an early detection method for metastatic breast cancer,” said El-Ashry, who is also associate professor of medicine. “Such knowledge would allow a patient and her doctors to work out the best therapeutic strategy. We are also determining if these CAFs may serve as a determinant of response to therapy. They may have direct therapeutic benefit, as novel treatments to target the circulating CAFs may mitigate metastasis and improve clinical outcomes for cancer patients.”

The implications of this work are promising, both as a non-invasive “liquid biopsy” that could tell a patient her risk for metastases or whether her tumor is responding to therapy, as well as CAFs acting as a therapeutic target. El-Ashry and her collaborators are currently seeking funding for clinical studies.

Co-authors on the article include Sylvester members Richard J. Cote, M.D., Professor and Joseph R. Coulter Chair of the Department of Pathology, professor of biochemistry and molecular biology, Chief of Pathology at Jackson Memorial Hospital, and Director of BioNIUM, Marc E. Lippman, M.D., Deputy Director of Sylvester and professor of medicine, and Ram H. Datar, Ph.D., associate professor of pathology, and biochemistry and molecular biology, and Co-Director of the Nanoscience Program, as well as graduate students Zheng Ao, Sanket H. Shah, Leah M. Machlin, Ritesh Parajuli, Philip C. Miller, Siddarth Rawal and Anthony J. Williams.

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