Researchers in the Department of Biomedicine at the University of Basel, Switzerland succeeded at converting breast cancer cells into fat cells. During trials of a combination therapy, the tumor cells were unable to form metastases in mice. Now it is hoped that the method can be applied to human clinical studies.
Tumor cells are extremely versatile: they turn into "nomads" who leave the primary tumor and will migrate to other parts of the body on the highway provided by circulation where they will then turn stationary and start forming metastases. An important role in the conversion of stationary to mobile cancer cells is played by a process that normally takes place in embryonic development and facilitates the emergence of organs. This cellular program is called epithelial mesenchymal transition or EMT and researchers headed by Gerhard Christofori utilized it to develop a novel therapeutic approach. EMT and the inverse process, mesenchymal-epithelial transition (MET), are implicated in cancer's ability to metastasize.
Relying on two known active ingredients the study published in Cancer Cell controlled the EMT program in mice in such a way that metastasizing breast cancer cells ultimately turned into fat cells. Converted cells cannot multiply and are barely distinguishable from ordinary fat cells. Above all, they can no longer metastasize. Cells undergoing EMT or MET are in a highly changeable state, providing a window of opportunity for therapeutic targeting. Active ingredients used were rosiglitazone, a drug used used against type 2 diabetes, and trametinib, used to restrict the growth and spread of cancer cells. In combination with conventional chemotherapy, these agents may be able to suppress growth of the primary tumor and simultaneously the formation of metastases: forcing a critical mass of cancerous cells to differentiate into fat cells could deplete a tumor's ability to fight off conventional chemotherapy. Of course, this will have to be tested by clinical studies in humans where, unfortunately, rosiglitazone has showed apparent associations with increased risk of heart attacks and death, calling for a careful complex risk assessment that will largely center on the duration requirements of combination therapy to secure against metastases.
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