Pending grant projects

CSF no.: P303/12/G163: Centre of drug-dietary supplements interactions and nutrigenetics

Period: 2012 – 2018

Dietary supplements containing natural compounds are increasingly popular. Dietary supplements became an alternative to classical medication and they are widely believed to be safe and without any adverse effects or interactions with drugs. However, some natural compounds present in high concentrations in dietary supplements are known to cause serious toxicities. Moreover, the toxicological profiles of certain supplements have not been systematically examined. The aim of the project is to evaluate interactions of selected natural constituents with drug-metabolizing enzymes, transporters and nuclear receptors to predict possible interactions with clinically relevant drugs and further characterize biological properties of the natural compounds and their metabolites. The influence of genetic predisposition on kinetics and adverse effects of these compounds will also be followed. Finally, we will provide recommendations for general population as well as for individuals with polymorphic biotransformation and predict idiosyncratic toxicity of the studied natural compounds.

AZV no.: 17-28470A: Importance of oxysterol signaling for endocrine therapy of breast carcinoma

Period: 2017 – 2020

In the frame of this project, we plan to evaluate importance of genetic and phenotypic markers of oxysterol signaling for endocrine therapy of breast carcinoma. In the long-term perspective, we expect significant socio-economic benefit for both patients and health care system with the use of these markers for prognosis and individualized therapy. This project also aims to elucidate mechanisms of action of validated markers and to determine cost-effective method for their screening. Results of the project will be published in impacted scientific journals, presented at specialized scientific meetings, and implemented into whole-life education programs for medical personnel. Scientists, lecturers and physicians in the area of experimental and clinical oncology and patients will be major users of the project results.

AZV No. 17-28231A: Expression of biotransformation enzymes in hepatocellular carcinoma

Period: 2017 – 2020

The project proposed aims at studying expression of biotransformation enzymes in primary liver cancer, namely hepatocellular carcinoma (HCC). Hepatocytes constitute approx. 80% of liver cell population and form a major biotransformation organ of the human body. Biotransformation affects drug levels by their metabolic inactivation/activation. HCC, i.e. primary hepatocyte malignancy, threatens the patient not only by tumor growth - malignant hepatocytes lose their metabolic capacity, which can affect the efficiency and toxicity of pharmacotherapy (incl. chemotherapy and targeted therapy). It is known that enzyme expression vanishes in cultivated primary hepatocytes and hepatic cancer cell lines. However, the expression of biotransformation enzymes in HCC has not been described in Caucasian population and has never been studied in the context of clinical data and pharmacotherapy.

AZV No. 16-28375A: Study of prognostic and predictive biomarkers in therapy of pancreatic carcinoma

Period: 2016 – 2019

The motive of this multidisciplinary research project is to obtain new knowledge in the field of predictive and prognostic biomarkers of pancreatic cancer, usable for rapid and economical screening of patients and for the treatment individualization. One of the aims is to establish the genetic profile of individual patients with pancreatic cancer using exome sequencing of specific genes of carcinogenesis and the division of patients into well-defined subgroups (molecular subtypes) with different biological behavior of the tumor. Another aim is to verify phenotypic profile of chemoresistance of pancreatic cancer observed in our previous studies by the analysis of gene and protein expressions and correlation of the results with different molecular subtypes. Partial aim is also to evaluate the mechanism of action of validated biomarkers using in silico prediction and functional tests.

AZV no.: 15-25618A: Validation of biomarkers of chemosensitivity of breast carcinoma

Period: 2015 – 2018

This project aims to validate recently identified genetic and phenotypic biomarkers of breast carcinoma chemoresistance. Anticipated use of these biomarkers for individualized therapy may bring significant socio-economic benefit for both patients and health care system. Mechanisms of action of validated biomarkers will also be elucidated and cost-effective methods for biomarker screening developed as other aims. Results of the project will be published in impacted scientific journals, presented at specialized scientific meetings, and implemented into whole-life education programs for medical personnel. Scientists in the area of experimental and clinical oncology and pharmacology, lecturers and professors at medical and life science schools, physicians, and patients will be among major users of the project results.