They provide new data on why treatment fails in the most aggressive brain tumors, which could be used to design new therapies
A team of scientists, in the
in which the University of Granada participates, has made progress in determining the causes why glioblastoma multiforme (GBM), one of the most aggressive brain tumors that exists, is resistant to the drugs currently used, one of the main limitations in its treatment. The results have recently been published in two articles in the journal PlosOne.
Researchers show that proteoglycans (structural elements of cells), called decorin (DCN) and lumican (LUM), could be instrumental in the behavior and development of resistance to drugs used to treat glioblastoma multiforme, such as temozolamide (TMZ). On the other hand, they have shown that the inhibition in the transcription of some of the subunits that are part of the “mismatchrepair (MMR) complex”, a system that recognizes and repairs errors in DNA, could participate in the failure of the current therapies against this type of tumor.
This important scientific advance could be relevant both for the search for new resistance markers in GBM and for the design of new therapeutic strategies that avoid drug resistance in these tumors.
The studies on glioblastoma stem cells have been carried out by researchers from the Institute of Biopathology and Regenerative Medicine (IBIMER) of the University of Granada and the Biosanitary Research Institute of Granada (Group A-01), in collaboration, on the one hand, with the Bellvitge Biomedical Research Institute of Barcelona, the Medical Oncology Service of the Granada University Hospital Complex and, on the other hand, with the National Institute of Biostructures and Biosystems (INBB) of Rome and the Department of Biomedical Sciences of the University of Sassari.
Low survival
GBM, the most frequent and aggressive tumors of the central nervous system, continue to present a low survival rate (less than a year and a half after diagnosis), despite the use of TMZ in combination with other drugs or radiotherapy, due, among other causes , to the development of resistance.
In the work in which the UGR participates, it is analyzed how the massive synergistic expression of DCN and LUM in GBM-derived stem cell neurospheres correlates with a lower proliferation rate of tumor cells and a lower development of apoptosis (a type of cell death that multicellular organisms use to eliminate damaged or unnecessary cells), but also with an increase in resistance to treatment with TMZ, one of the key drugs in the current treatment of these patients.
On the other hand, studies carried out in drug-exposed lines of glioblastoma and neuroblastoma demonstrate how resistance to TMZ is not only mediated by the classical mechanism of the DNA repair enzyme MGMT, but is also related to the silencing of the MMR complex. after drug exposure.
Studies are now focused on demonstrating the relevance of these two molecules in the behavior of glioblastomas 'in vivo' and analyzing the resistance mechanism based on the MMR complex in this same system.
Bibliographic references:
Perazzoli G. et al. (2015) Temozolomide Resistance in Glioblastoma Cell Lines: Implication of
MGMT, MMR, P-Glycoprotein and CD133 Expression.
PLoS ONE 10 (10): e0140131.
doi: 10.1371 / journal.pone.0140131
Farace C. et al. (2015) Microenvironmental Modulation of Decorin and Lumican in
Temozolomide-Resistant Glioblastoma and Neuroblastoma Cancer Stem-Like Cells.
PLoSONE 10 (7): e0134111. doi:
10.1371 / journal.pone.0134111.
The full articles are
available at the following links:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4598115/
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4521885/
Contact:
Jose Carlos Prados Salazar
Professor of the Department of
Human Anatomy and Embryology. Institute of Pathology and Medicine
Regenerative of the University of Granada.
Phone: 958248819; 958241000
ext. 20015/20032
E-mail:
jcprados@ugr.es