Projects / Programmes source: ARIS

The role of genetic polymorphisms in treatment result and occurance of side effects in children with cancer

Research activity

Code Science Field Subfield
3.04.00  Medical sciences  Oncology   

Code Science Field
B660  Biomedical sciences  Pediatrics 

Code Science Field
3.02  Medical and Health Sciences  Clinical medicine 
pediatric oncology, vincristine, polyneuropathy, genetic polymorphisms
Evaluation (rules)
source: COBISS
Researchers (24)
no. Code Name and surname Research area Role Period No. of publicationsNo. of publications
1.  32191  Simona Lucija Avčin  Oncology  Researcher  2011 - 2014  44 
2.  19258  PhD Tadej Avčin  Human reproduction  Researcher  2011 - 2014  463 
3.  03564  Majda Benedik Dolničar  Human reproduction  Researcher  2011 - 2014  191 
4.  00781  PhD Borut Božič  Microbiology and immunology  Researcher  2012 - 2014  600 
5.  15657  PhD Maruša Debeljak  Oncology  Researcher  2011 - 2014  238 
6.  31879  Petra Ferkov    Technical associate  2013 
7.  32034  PhD Martina Gobec  Oncology  Junior researcher  2011  170 
8.  10972  PhD Janez Jazbec  Oncology  Head  2011 - 2014  314 
9.  27741  PhD Simona Jurković Mlakar  Pharmacy  Researcher  2012  82 
10.  21459  PhD Nataša Karas Kuželički  Pharmacy  Researcher  2012 - 2014  169 
11.  32049  PhD Marko Kavčič  Oncology  Researcher  2011 - 2014  62 
12.  19257  PhD Lidija Kitanovski  Oncology  Researcher  2011 - 2014  150 
13.  10648  MSc Matevž Kržan  Neurobiology  Researcher  2011 - 2014  96 
14.  34223  PhD Tijana Markovič  Pharmacy  Researcher  2011 - 2014  58 
15.  12443  PhD Irena Mlinarič Raščan  Pharmacy  Researcher  2011 - 2014  528 
16.  36767  Tomaž Prelog  Oncology  Researcher  2014  23 
17.  29602  PhD Matevž Prijatelj  Pharmacy  Junior researcher  2011  32 
18.  32593  PhD Vladan Rajić  Oncology  Researcher  2011 - 2014  70 
19.  23549  PhD Robert Roškar  Pharmacy  Researcher  2012  297 
20.  08752  PhD Saša Šega Jazbec  Cardiovascular system  Researcher  2011 - 2014  199 
21.  29982  PhD Alenka Šmid  Pharmacy  Researcher  2012 - 2014  121 
22.  20128  PhD Alenka Trampuš Bakija  Cardiovascular system  Researcher  2011 - 2014  124 
23.  34512  PhD Dunja Urbančič  Pharmacy  Junior researcher  2011 - 2014  55 
24.  29810  Tina Vesel  Microbiology and immunology  Researcher  2011 - 2013  64 
Organisations (2)
no. Code Research organisation City Registration number No. of publicationsNo. of publications
1.  0312  University Medical Centre Ljubljana  Ljubljana  5057272000  75,485 
2.  0787  University of Ljubljana, Faculty of Pharmacy  Ljubljana  1626973  17,150 
Although an enormous progress was achieved in the survival rate of childhood cancer, still in some 40 % of all cases the outcome is fatal. A possible way of further improvement is individualization of treatment protocols by distinguishing patients with better tolerance of high dose chemotherapy from those who are more prone to severe toxic events in advance.   Vincristine, a chemotherapeutic agent, is widely used in combination with other agents in the treatment of pediatric haematological malignancies and solid tumors. The most established mechanism by which vincristine inhibits tumor growth is its interference with mitotic spindle microtubules resulting in inhibition of mitosis. Patients treated with vincristine predictably develop peripheral neuropathy which is a major dose-limiting side effect of vincristine. In children treated with identical treatment protocols containing vincristine, the severity of peripheral neuropathy varies greatly. Peripheral neuropathy may be related to polymorphisms in genes involved in vincristine pharmacokinetics or pharmacodynamics: metabolising gene or vincristine toxicity related genes.   Every year we diagnose around 60-70 new patients with childhood cancer in Slovenia. In two years we expect to include around 90 patients with vincristine regimen in their treatment protocol. In all patients we will monitor all possible acute toxicities. In our study we will stratify patients based on signs of standardised clinical neurological examination and parameters of standardized electrophysiological examination according to the severity of vincristine induced peripheral neuropathy. We will genotype DNA from mononuclear blood cells for polymorphisms of vincristine metabolising gene (CYP3A5) or vincristine toxicity related genes (MDR-1 and MAPT).   Based on the results of genetic polymorphism of target genes we expect that we will be able to predict the risk for development of peripheral neuropathy in children treated for cancer. These results may reveal subpopulation of patients with increased risk for peripheral neuropathy after the treatment with vincristine. We could also define group of patients, which may tolerate higher doses of Vincristine in whom intensification of vincristine chemotherapy regime may improve survival of children treated for cancer. The final perspective of all pharmacogenetic studies is therapy individualization. By finding a patient-specific “optimal” dose, we could balance the risk of relapse and the risk of severe adverse effects more precisely.
Significance for science
Pharamacogenetics is a quickly improving field of molecular genetics. The individual differences in the drug metabolism, pharmacokinetics and pharmacodynamics contribute to the efficacy and safety of any pharmacotherapy. Since in hematology and oncology very toxic and predominantly high-dose chemotherapy regimens are used, pharmacogenetics can provide useful information for better patient care. With the results of our research project we followed the trends and came closer to personalised therapy of children with cancer. Altogether, we published more than 30 peer reviewed papers in journals indexed by SCI. Also, three members of our research group successfully finished their doctoral thesis.
Significance for the country
With the successful international collaboration we managed to transfer top science to our research community. We developed a research infrastructure which include top foreign scientists and enable us to collaborate in everyday clinical decision making as well as in developing future research strategies. We contributed to interdisciplinary research on the pediatric oncology field. Importantly, we claim that the results of our research project have a direct effect to improve the care of children treated for cancer on The department for pediatric hematology and oncology of The University Pediatric Hospital in Ljubljana.
Most important scientific results Annual report 2011, 2012, 2013, final report, complete report on dLib.si
Most important socioeconomically and culturally relevant results Annual report 2011, 2012, 2013, final report, complete report on dLib.si
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