A European team has managed to overcome the resistance of cancer cells to chemotherapy, by combining an antifungal agent with a cancer drug. The team was made up of researchers from the Pushkin Academy of Science in Moscow and Salzburg University and was coordinated by the Yeast Molecular Genetics Laboratory at the International Centre for Genetic Engineering and Biotechnology (ICGEB), operating at AREA Science Park in Trieste under the guidance of Professor Carlo Bruschi.

The study, published in this month's edition of the European Journal of Cell Biology, examined two conventional chemotherapy treatments. It emerged that resistance to cancer drugs comes from the abnormal expression of certain proteins (PRK1, PDR1 and PDR3) related to the structure of the cell's cytoskeleton, which determines cell permeability. Drug resistance is now the greatest limitation on the use of drugs in chemotherapy cycles. The model for the research was Saccharomyces cerevisiae, an ordinary cell from the yeast used in breadmaking. This eukaryotic microorganism is seen by biotechnologists as being almost essential in identifying specific functions in human cell mechanisms.

A new combination of two cancer drugs, Doxorubicin and Latrunculin-A, and the antifungal agent Amphotericin B, has passed laboratory tests on drug resistance, one of the main causes of failure in cancer treatment

The fusions of chromosomes, also known as chromosomic translocations, are genetic anomalies closely linked to the appearance of cancerous cells, as in the case of chronic myeloid leukaemia. By studying new techniques of artificially-induced chromosomic translocation, Dmitri Nikitin from the Moscow Academy of Science, a post-doctoral student at the ICGEB and the first author of the study, discovered that this type of event makes yeast cells resistant to Doxorubicin and Latrunculin-A, two well-known cancer drugs used in clinical oncology.

Researchers used this observation to work on overcoming the resistance to the two drugs, by resorting simultaneously to a third drug, the well-known antifungal treatment Amphotericin B, already used to treat mycosis in humans. At high doses, Amphotericin B is toxic to the auditory system, but when sub-toxic doses are allowed to penetrate the cell, it can not only inhibit drug resistance but even reinforce the oncosuppressive effect of the two cancer drugs.

"Last year, we published a highly successful review in the journal Frontiers, on the now universal use of yeast as a model for cancer cells" explained Valentina Tosato, the author of the review and of previous works on chromosomic translocations. Discovering that this microorganism is subject to the same drug resistance as human cells not only reinforces its value as a model, but also gives us the opportunity to explore this area much more deeply. We hope that our work will help people who are using chemotherapy drugs to fight cancer".

"I cannot deny that I am extremely pleased about the publication of this study", enthused Carlo Bruschi, Senior Scientist at the ICGEB. "It comes at the end of a long and rather complex journey, given the potential implications in terms of changes to the most common procedures used in treating cancer. It was a good example of teamwork, and the results will not only expand our knowledge of cancer-related cell mechanisms, but may also have great importance from a clinical viewpoint".