What are the main goals of this research programme of the NICR? How well are they being met? What successes did your colleagues and groups involved in research in the area of early detection and prevention of tumours already achieve? You will find answers to these questions and more in an article prepared by heads of this programme, Petr Džubák and Marek Svoboda.
Research programme 4 (RP4) – Early detection and prevention of tumours – is one of the key areas of activity of the NICR. Its goal is to develop innovative methods and technologies for early diagnosis of cancers and identification of risk factors that would enhance the effectiveness of screening programmes, improve treatment outcomes, and ultimately decrease patients’ morbidity thanks to early tumour detection. Early detection of tumours makes it possible to start targeted therapy at a stage when the disease is best treatable, which in turn improves the patient’s chance of a full recovery.
We have a multidisciplinary team composed of leading experts from academic institutions and the clinical sphere that works towards meeting these targets. Involved in the programme are especially institutions of the Palacký University in Olomouc, including the Institute of Molecular and Translational Medicine, Masaryk Institute of Oncology in Brno, and the First Faculty of Medicine of the Charles University in Prague. A unique synergy of experts in molecular biology, genetics, bioinformatics, analytical chemistry, biophysics, and medicine facilitates a comprehensive approach to early tumour detection.
Protein signature and early detection of lung cancer
One of the cornerstones of currently ongoing research is a large multicentric study led by the Institute of Molecular and Translational Medicine in Olomouc, which focuses on the identification of biomarkers of lung cancer in the condensate of exhaled air. The target group are especially individuals who at a high risk of lung tumours, including active smokers and former heavy smokers. This study directly follows up on a successful pilot project whose outcome was a characterisation of the protein spectrum (protein signature) specific for bronchial and lung tumours. The aim of the current study is to validate the protein signature for the purpose of early detection of lung cancers in larger patient and control (healthy) cohorts. We believe that the study will provide enough data to help us decide whether this is a sufficiently robust method suitable for oncological screening and whether it could be implemented in clinical practice. Success of this study could improve the effectiveness of screening for lung tumours. Healthcare facilities across Czech Republic are gradually becoming involved in sampling and data collection (University Hospital Olomouc, Masaryk Institute of Oncology, General University Hospital in Prague, and more).
A new biochip method for detection of mutation V600E in the BRAF gene
Concurrently with clinical research, we are also engaged in developing a highly sensitive method for detection of tumour-specific biomarkers. Teams from the NICR use the most advanced technologies – such as Raman spectroscopy, surface plasmon resonance, or electrochemical chips – that enable the detection of even very low concentrations of protein and genetic markets in easily accessible body fluids. A great advantage of these methods is their potential for use in clinical environment, including routine examinations.
One of our most notable partial successes is the development of a new biochip method for the detection of mutation V600E in the BRAF gene, which is the key activation mutation in the pathogenesis of numerous tumours, including the melanoma and cancers of the lungs or colon and rectum. The method developed by Martin Bartošík’s team at the Masaryk Institute of Oncology in Brno in collaboration with Universidad Complutense de Madrid, Spain, is highly sensitive and highly specific. It is optimised for analysis of so-called liquid biopsy, i.e., for detecting the mutation in the circulating tumour DNA isolated from patient’s blood sample. This opens the way to use in clinical practice, for instance as part of tertiary prevention for monitoring patients after treatment, which aims at early detection of eventual relapse of the disease. The results of this study were published in the prestigious journal Sensors and Actuators B: Chemical (IF 8,4). The method is now also registered for a patent process, which attests to its innovativeness and application potential (Sebuyoya et al., 2023).
ENIGMA: Extensive functional analysis of missense variants of the CHEK2 gene
We have also achieved progress in the area of identification of genetic predictors of the occurrence of cancers. This is a highly important area of research whose results can have a crucial impact on the stratification of risks and rational setting of preventive programmes for individuals who carry pathogenic mutations in genes that play a role in the development of the hereditary cancer syndrome. In collaboration with the ENIGMA international consortium, we have completed an extensive functional analysis of missense variants of the CHEK2 gene, one of the most frequently mutated genes in persons who are tested because of suspicion of hereditary cancer syndrome. A study of an international team led by experts from the First Faculty of Medicine of the Charles University, published in the Clinical Cancer Research journal, had shown that some missense variants are linked to a medium-sized increase in the risk of breast cancer and are therefore of great importance for clinical practice in terms of genetic testing and consulting about preventive measures (Stolarova et al., 2023).
Research that takes place as part of RP4 can have a significant impact on care for both cancer patients and healthy population. The development of new, more accurate, and more accessible methods of early diagnostics can enable us to detect cancers during curable stages, while identification of individuals who are at an increased genetic risk opens the way to personalised preventive programmes. Such results can shift the potential of both prevention and personalised care onto a new level, leading to improved quality of life and a reduction of the social and economic impact of cancers.
References
Sebuyoya, R., Valverde, A., Moranova, L., Strmiskova, J., Hrstka, R., Montiel, V. R.-V., Pingarrón, J. M., Barderas, R., Campuzano, S., & Bartosik, M. (2023). Dual detection system for cancer-associated point mutations assisted by a multiplexed LNA-based amperometric bioplatform coupled with rolling circle amplification. Sensors and Actuators B: Chemical, 394, 134375. https://doi.org/10.1016/j.snb.2023.134375
Stolarova, L., Kleiblova, P., Zemankova, P., Stastna, B., Janatova, M., Soukupova, J., Achatz, M. I., Ambrosone, C., Apostolou, P., Arun, B. K., Auer, P., Barnard, M., Bertelsen, B., Japan, B., Blok, M. J., Boddicker, N., Brunet, J., Burnside, E. S., Calvello, M., … Kleibl, Z. (2023). ENIGMA CHEK2gether Project: A Comprehensive Study Identifies Functionally Impaired CHEK2 Germline Missense Variants Associated with Increased Breast Cancer Risk. Clinical Cancer Research, 29(16), 3037–3050. https://doi.org/10.1158/1078-0432.CCR-23-0212