New Ways to Target Harmful Proteins in Cancerous Cells Developed at UNIGE
The scientists at the University
of Geneva (UNIGE) have developed an innovative method to target harmful protein
FKBP10 in lung and colon cancers. The new therapeutic treatment inhibits the
growth of these harmful proteins that promote cancer-stem cells and extremely
reisistant. It was done with an animal model of lung cancer and with
The FKBP10 protein was identified by Roberto Coppari, Professor in the Department of Cell Physiology and Metabolism at UNIGE Faculty of Medicine in 2014. Such proteins are expressed in human lung cancer cells but not in healthy cells.
To test the role of FKBP10 in cancer progression, the researchers studied a mouse model of lung cancer. “The inhibition of FKBP10 expression in some of our mice, particularly after tumour development, led to the near disappearance of cancer”, says Coppari. “This confirms, in a whole organism, the results we had previously obtained with human cancer cells. It also shows, and this is really important from a therapeutic point of view, that the process can be reversed after cancer onset.”
Furthermore, FKBP10 also appears to be involved in the high risk of relapse: a few months or years after an initial apparently effective treatment, the tumour may return very aggressively. “Resistance comes from so-called “cancer stem cells” that have a very specific profile”, says Martine Collart, Professor in the Department of Microbiology and Molecular Medicine at UNIGE Faculty of Medicine, whose expertise in protein synthesis and assembly has proved essential. “Treatments generally aim at destroying rapidly dividing cells, as are most tumour cells. However, cancer stem cells can escape because they do not divide rapidly. They can be even selected and enriched by chemotherapies before becoming capable of proliferating, and then induce relapse in an even more aggressive form. In this context, FKBP10 appears to be important for protein synthesis and particularly upon insertion of an amino acid called proline. Hence, by inhibiting FKBP10 we not only arrested proliferation of cancer cells but also hindered the formation of cancer stem cells.” Indeed, in order to be able to assume their function in cells, proteins must fold correctly after synthesis. This phenomenon is linked to the way in which the amino acids are arranged. One of them, proline, can adopt different configurations, and thus allow proper folding and function of proteins in which it is incorporated, or not. And FKBP10 changes the isomerisation of proline – the way it is configured – in proteins.
Roberto Coppari is in the process of reanalysing dozens of drugs already approved in order to test their effect on FKBP10, in the hope of identifying an effective exact characterization of the protein to target it specifically. “We are addressing the same issue in a different way in order to combine them for greater efficacy”, the authors conclude.