Breast cancer treatment and the mechanical properties of fibroblasts

In breast cancer, the amount of extracellular stroma is an indicator of poor prognosis. Fibroblasts that produce the extracellular matrix, and they are often present in the stroma at all stages of cancer development, from the inception and establishment of the primary tumour, during tumor cell invasion and dormancy until the last stage of cancer cell metastasis, and they control the chemical composition, spatial organisation and mechanical properties of the stroma. While normal fibroblasts inhibit the growth of cancer cells, this inhibitory activity can be lost, and even reversed, to an opposing tumour-stimulatory activity of cancer-associated fibroblasts.

We will use the cells to determine the mechanical difference between normal and cancer-associated fibroblasts, and to determine how the fibroblasts interact mechanically with the tumour epithelial cells, and identify the underlying molecular control. The molecular mechanisms that govern the mechanical properties of CAFs will be considered target biomarker molecules for the future development of anti-cancer drugs.

The identification of a previously unknown, mechano-based class of target proteins for the development of drugs that block triple-negative breast cancer, can increase the diversity and efficiency of treatment, and improve prevention of human death in cancer. In the long term, the findings can also contribute to the development of novel diagnostic methods that are based on analyses of the nanomechanical differences between normal and CAFs.