21.05.2014 -
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".