Institute of Experimental Medicine CAS

Published 27. 04. 2022

Research projects of Mgr. Michal Kroupa, PhD and RNDr. Soňa Vodenková, PhD have succeeded in a public competition for financial support from the Ministry of Health of the Czech Republic (MZČR) and received the "AZV Junior" grant. 

Both scientists succeeded in a strong competition of 60 junior projects, from which only 12 projects were selected and recommended for funding. 

The Czech health research council (AZV) evaluated the individual project proposals, and subsequently recommended the selected projects for funding by the MZČR. The total allocation of funds amounts to 81 324 000 CZK (for the entire project duration), with 14 282 000 CZK allocated for 2022. 

The following projects were selected for the IEM CAS: 

Significance of mitochondrial DNA in colorectal cancer
RNDr. Soňa Vodenková, PhD - Department of the Molecular Biology of Cancer  

Development of genomic instability and disruption of telomere integrity in colorectal cancer
Mgr. Michal Kroupa, PhD - Department of the Molecular Biology of Cancer

The above projects will be implemented in cooperation with the Biomedical Centre of the Medical Faculty of Charles University in Pilsen. The research results should lead to higher personalisation of diagnostics and treatment of oncological patients. 

Personalised cancer care takes advantage of the fact that tumours carry genetic changes and characteristics that we can now diagnose. It is based on detailed knowledge of the features of the disease in a particular patient. This makes it possible to prolong patients' lives and improve their quality of life, i.e. less unnecessary treatment, fewer side effects and associated costs through informed decisions about whether, when and how to treat a patient. 

Development of genomic instability and disruption of telomere integrity in colorectal cancer

Mgr. Michal Kroupa, PhD - Department of the Molecular Biology of Cancer  

Colorectal cancer (CRC) is one of the most frequently diagnosed cancers in the Czech Republic. A characteristic feature of CRC is a disturbance of genomic stability manifested most often in chromosomal or microsatellite instability. It is currently assumed that the two phenotypes are not mutually exclusive and that there may be a partial overlap between them. As both phenotypes are associated with specific treatments, the question remains as to what extent are both manifested within a tumor from a single patient. 

The second part of the project focuses on comparing differences/matches in genomic instability and differences/matches in telomere biology in the transition from the primary tumor to metastatic tissue. Simply, what the metastatic tissue inherits from the tumor and what is newly generated in the metastasis (the genetic matches/differences) in a particular patient (scientists have primary tumor tissue and metastatic tissue from the same patients).

The aims of the project are to find out: 

• Does possible concordance or specific patterns in DNA copy number alternations between primary tumors and corresponding metastatic lesions of patients with colorectal cancer exist? 
• Do multiple genomic instability phenotypes coexist within a tumor tissue? (i.e. are hypermutated tumors with microsatellite instability and/or metastasis karyotypically heterogenous)? 
• Is microsatellite instability phenotype and/or colorectal cancer dissemination connected with telomerase repression and can it switch to the alternative lengthening of the telomeres mechanism?

This research could help to improve the personalisation of cancer treatment (as chromosomal and microsatellite instability phenotypes are associated with specific therapies, and telomere-targeted therapeutics are being tested).

The importance of mitochondrial DNA in colorectal cancer

RNDr. Soňa Vodenková, PhD - Department of the Molecular Biology of Cancer  

In this project, we will focus on studying mitochondrial DNA (mtDNA) and its changes in patients with newly diagnosed sporadic colorectal cancer (CRC). Mitochondria are key organelles of eukaryotic cells responsible for numerous essential cellular functions, including, among others, ATP production through oxidative phosphorylation and induction of apoptosis. The number of mitochondria in a cell depends on its energy demand; they are especially highly present in cells with high energy requirements. 

Mitochondria play an important role in the incidence and development of cancer cells, participating in cell proliferation, apoptosis and ageing. Since mitochondria contain their DNA, they could serve as a candidate marker to better understand CRC pathogenesis and progression. Changes in mtDNA have already been identified in several types of solid cancers, but their impact on the course of the disease, patients’ prognosis, and treatment response remains unclear. Likewise, the clinical significance of mtDNA in the blood plasma of cancer patients has not been elucidated. 

Our project intends to determine the amount of mtDNA in tumor tissue, adjacent non-tumor mucosa, and blood and also characterize variations, damage, and repair of mtDNA. We will analyze the obtained data together with the clinical characteristics of patients. Patients will be further monitored to assess the impact of received data on the efficacy of anticancer therapy, patients’ prognosis, and long-term survival. 

The results of the project could contribute to a better determination of patients’ clinical characteristics.