Researchers at Lund University and Karolinska Institutet have uncovered a way to treat aggressive breast tumors through manipulation of the connective tissue cells of the tumor. The researchers are now developing a new drug that transforms aggressive breast cancer so that it becomes responsive to standard hormone therapy. The findings are published in Nature Medicine.
Approximately 10-15 per cent of breast cancer patients have so-called basal breast cancer that do not respond to treatment with hormone therapy, which means that they are more aggressive and often recur.
Recent studies emphasize the importance of the communication of cancer cells with other cell types in the surrounding tissue, such as connective tissue, blood vessels and immune system cells, enabling the tumors to form, spread and resist treatment. In the new study, researchers have revealed a growth factor - PDGF-CC - which transmits information between the tumor cells and the connective tissue cells, mainly in basal breast cancers.
"Detailed analyses of around 1,400 breast cancers showed that high levels of PDGF-CC in the tumor cells were associated with a poor prognosis", explains Kristian Pietras, Professor at Lund University.
He led a multidisciplinary and international research team based at the Lund University Cancer Centre at Medicon Village, in collaboration with researchers from Karolinska Institutet, the Olivia Newton-John Cancer Research Institute in Melbourne, Australia, and University Hospital Bonn.
"Previously, it was believed that the various subgroups of breast cancer originated from different cell types in the mammary gland. Our research has shown that connective tissue cells can also modify tumor cells directly with regard to their sensitivity to hormones, which has significant implications in the development of more effective treatments", says Professor Ulf Eriksson at Karolinska Institutet's Department of Medical Biochemistry and Biophysics, who initiated the study together with Professor Pietras.
New biological drug
In experimental models, the researchers tested a new biological drug that they have developed, which blocks the PDGF-CC-mediated communication between the tumor cells and the connective tissue cells. This resulted in the transformation of the basal breast cancers into hormone-sensitive (luminal) breast cancers. As a consequence, the tumors then became highly responsive to conventional hormone therapy.
"We were also able to show the opposite; that a hormone-sensitive breast cancer can be transformed into a more aggressive, difficult-to-treat cancer if it is able to communicate with connective tissue cells through PDGF-CC", says Hong Li, researcher in Ulf Eriksson's research group at Karolinska Institutet.