18. 04. 2024
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We would like to share with you the success of two of our postdoctoral researchers – Klára Vokáčová from the Department of Molecular Biology of Cancer and Marek Ladislav from the Department of Neurochemistry,
who have succeeded in a public competition for special-purpose support from the Ministry of Health of the Czech Republic in research, experimental development and innovation for the years 2024 – 2027.
Both scientists were successful in a strong competition of 440 projects, from which 96 projects, including 15 junior projects, were selected and recommended for funding. The individual proposals were evaluated by the Czech Health Research Council (open in a new window), which later recommended the selected projects for funding by the Ministry of Health of the Czech Republic. The total allocation of funds amounts to CZK 1,173,685,000 for the entire duration of the projects.
The project “The predictive value of circulating biomarkers for complete pathological response after total neoadjuvant radiochemotherapy of rectal cancer“, of which Klára is a co-investigator, will be realised in collaboration with Palacký University in Olomouc and the Faculty Hospital Olomouc. The principal investigator is Dr. Radmila Lemstrová. The second successful project is Mark’s project, focused on “Exploring the therapeutic potential of ketamine enantiomers to address attentional and cognitive impairments in GRIN-related disorder model“. Detailed descriptions of both projects can be found below.
We would like to congratulate both of our scientists and wish them good luck and much success in their research.
Projects description
The predictive value of circulating biomarkers for complete pathological response after total neoadjuvant radiochemotherapy of rectal cancer
Total neoadjuvant radiochemotherapy (TNT) followed by total mesorectal excision is a new standard of care for patients with locally advanced rectal cancer. Several prospective randomised trials have demonstrated the efficacy of TNT in terms of a double increase in pathological complete remission (pCR) rates and reduction of distant metastasis. The increased rates of pCR have raised a novel approach of organ preservation known as the “watch and wait” (W&W) strategy, avoiding the complications of surgery and improving the quality of the patient´s life. Nevertheless an evaluation of the treatment response by imaging modalities is quite challenging due to the tissue changes after TNT. There is an urgent need for effective predictive biomarkers for pCR to specify the selection of the eligible patients for W&W strategy and to individualise the neoadjuvant treatment with regard to the toxicity. Liquid biopsy can be defined as the collection and analysis of biomarkers derived from the tumour but present in blood or other body fluids. It offers several advantages such as the possibility of repeated sample collection and the associated real-time disease monitoring, minimal invasiveness and low cost.
The aim of the project is to investigate the circulating tumour DNA and non-coding RNAs as promising predictive circulating biomarkers of TNT and pCR. The aim of the project is to assess the predictive value of the circulating biomarkers for pathological complete response (pCR) after total neoadjuvant radiochemotherapy (TNT) for locally advanced rectal cancer as follows:
- Quantification of plasma ctDNA concentration variances and expression of specific mutations (TP53, BRAF, KRAS) in the pre-treatment, treatment and post- treatment period of TNT and determination of the predictive value for pCR.
- Investigation of TNT impact on the expression levels of miR-122-5p and miR-142-5p and determination of the predictive value for pCR.
- Forming a pCR predictive model of high accuracy for clinical practice on the basis of miRNA expression levels, ctDNA concentration variances, clearance of specific mutations and results of imaging modalities such as magnetic resonance and endoscopy.
Exploring the therapeutic potential of ketamine enantiomers to address attentional and cognitive impairments in GRIN-related disorder model
Neurodevelopmental disorders, particularly a subset of GRIN-related disorders (GRDs), pose unique challenges due to genetic mutations that affect how certain brain receptors, known as NMDARs, function. These mutations lead to a specific problem: they make NMDARs too active, missing a natural stopping mechanism, which results in a range of issues, from learning difficulties to problems with speech and muscle tone. This overactivity is particularly due to mutations in a part of the receptor known as the M2 loop, crucial for the receptor’s normal operation.
While current treatments for GRDs mainly manage symptoms, our project seeks to close this gap with a pioneering approach. We’re exploring the use of ketamine, a medication known for its effectiveness in treating depression, as a potential remedy. Our focus narrows down to a specific mutation within the M2 loop, utilising a mouse model engineered to replicate this unique genetic condition. This targeted exploration allows us to understand how ketamine might reset these overly active receptors to their proper function.
The core of our mission is to dissect the interaction between ketamine and these specific receptors influenced by the M2 loop mutation. Our goal is to see whether this interaction can alleviate the cognitive and attentional deficits associated with this distinct GRD subclass. Through comparative analyses of the effects of ketamine on both mutated and normal receptors, we’re on the path to demonstrating ketamine’s capacity as a precise and impactful treatment.
This initiative is more than just a scientific endeavour; it’s a step toward opening new doors for personalised medicine. By targeting treatments to the specific genetic profiles of individuals, we aim to offer not just hope but a tangible improvement in the quality of life for those affected by these targeted neurodevelopmental disorders. This research not only promises to advance our understanding of GRDs but also to pioneer new, more effective ways of addressing them.