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.
