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The three pillars of a NICR research programme focused on translational oncology presented by Pavel Klener jointly with the programme\u2019s main leader, Ludmila Boubl\u00edkov\u00e1, are: First, a research of primary tumour cells, which \u2013 if we know the clinical parameters \u2013 can help us discover the genetic changes responsible for therapy resistance or cancer relapse. Second, testing of experimental drugs in proof-of-concept preclinical studies using cell lines or mouse models. And finally, a validation of biomarkers of effectiveness or resistance to the tested treatment in the early stages of clinical studies involving patients.\u00a0<\/b><\/b><\/p>\n
A number of respected experts from both the academia and the clinical sphere are taking part in addressing the goals of Research Programme 5 (RP5), which focuses on translational oncology. Involved in the programme are institutes and groups from the First Faculty of Medicine of the Charles University, the Palacky University in Olomouc, Institute of Macromolecular Chemistry of the CAS, but also others. A unique synergy of experts from molecular biology, genetics, bioinformatics, macromolecular chemistry, and clinical medicine leads to a comprehensive approach to the development and preclinical testing of new drugs and therapies.<\/span><\/b><\/p>\n The first pillar of RP5 is a direct study of tumour (lymphoma and leucaemia) cells acquired from patients, so-called primary cells. These are cancer cells from the blood, bone marrow, tumour exudates, or tissues infiltrated by a tumour that have been acquired by biopsy or during surgical procedures (naturally with patients\u2019 consent). Given a knowledge of clinical parameters, research of primary cells can enable us to identify various genetic changes (mutations, deletions, amplifications, translocations) responsible for treatment resistance or cancer relapse. This can in turn lead to a better stratification of patients prior to the start of therapy and to a personalisation of treatment (1).<\/span><\/p>\n Most recent molecular-biological approaches, including single-cell sequencing or optic genomic mapping, moreover enable analysis of tumour populations on a sub-clonal level, that is, with a much greater level of detail than an analysis of tumour bulk can deliver. Single-cell approaches also enable a separate analysis of the non-tumour elements of the tumour microenvironment, which had been previously possible only to a limited extent. This advanced research can then generate new possible therapeutic targets, i.e., druggable targets.\u00a0<\/span><\/p>\n The second pillar of translational oncology are proof-of-concept preclinical studies, usually done <\/span>in vitro <\/span><\/i>using panels of cell lines and <\/span>in vivo <\/span><\/i>using mouse models, including experimental therapy of mice that carry patient-derived xenografts (PDX) (2,3). Mouse models moreover enable researchers to study even substances and therapeutical combinations that can be investigated <\/span>in vitro <\/span><\/i>only to a very limited extent (this applies for instance to therapeutical monoclonal antibodies or to so-called prodrugs). In order to conduct a relevant study of preclinical effectivity of experimental drugs, one must have at one\u2019s disposal some relevant preclinical models, that is, cell lines and PDX models. Derivation and characterisation of new lymphoma or leucaemia lines and PDX models is therefore another long-term direction of cancer research (4).<\/span><\/p>\n The third pillar of translational oncology consists of early-stage clinical trials with patients and translational research of biomarkers indicating treatment effectivity or resistance during these studies.<\/span><\/p>\n <\/p>\n Reference<\/span><\/i><\/p>\n Karolov\u00e1 J, Kazantsev D, Svato\u0148 M, Tu\u0161kov\u00e1 L, Forsterov\u00e1 K, Mal\u00e1rikov\u00e1 D, et al. Sequencing-based analysis of clonal evolution of 25 mantle cell lymphoma patients at diagnosis and after failure of standard immunochemotherapy. American journal of hematology. 2023;98(10):1627-36. DOI: <\/span><\/i>10.1002\/ajh.27044<\/span><\/i><\/a><\/p>\n Dolnikova A, Kazantsev D, Klanova M, Pokorna E, Sovilj D, Kelemen CD, et al. Blockage of BCL-XL overcomes venetoclax resistance across BCL2-positive lymphoid malignancies irrespective of BIM status. Blood advances. 2024. DOI: <\/span><\/i>10.1182\/bloodadvances.2024012906<\/span><\/i><\/a><\/p>\n Malarikova D, Jorda R, Kupcova K, Senavova J, Dolnikova A, Pokorna E, et al. Cyclin dependent kinase 4\/6 inhibitor palbociclib synergizes with BCL2 inhibitor venetoclax in experimental models of mantle cell lymphoma without RB1 deletion. Exp Hematol Oncol. 2024;13(1):34. DOI: <\/span><\/i>10.1186\/s40164-024-00499-2<\/span><\/i><\/a><\/p>\n Jak\u0161a R, Karolov\u00e1 J, Svato\u0148 M, Kazantsev D, Grajciarov\u00e1 M, Pokorn\u00e1 E, et al. Complex genetic and histopathological study of 15 patient-derived xenografts of aggressive lymphomas. Lab Invest. 2022;102(9):957-65. DOI: <\/span><\/i>10.1038\/s41374-022-00784-w<\/span><\/i><\/a><\/p>\n <\/p>\n","protected":false},"excerpt":{"rendered":" The three pillars of a NICR research programme focused on translational oncology presented by Pavel Klener jointly with the programme\u2019s main leader, Ludmila Boubl\u00edkov\u00e1, are: First, a research of primary tumour cells, which \u2013 if we know the clinical parameters \u2013 can help us discover the genetic changes responsible for therapy resistance or cancer relapse.<\/p>\n","protected":false},"author":3,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[100,78,84],"tags":[],"class_list":["post-3066","post","type-post","status-publish","format-standard","hentry","category-2024-3","category-newsletter-inscider-en","category-sciprogramme-newsletter-inscider-en"],"acf":[],"_links":{"self":[{"href":"https:\/\/www.nuvr.cz\/en\/wp-json\/wp\/v2\/posts\/3066","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.nuvr.cz\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.nuvr.cz\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.nuvr.cz\/en\/wp-json\/wp\/v2\/users\/3"}],"replies":[{"embeddable":true,"href":"https:\/\/www.nuvr.cz\/en\/wp-json\/wp\/v2\/comments?post=3066"}],"version-history":[{"count":4,"href":"https:\/\/www.nuvr.cz\/en\/wp-json\/wp\/v2\/posts\/3066\/revisions"}],"predecessor-version":[{"id":3377,"href":"https:\/\/www.nuvr.cz\/en\/wp-json\/wp\/v2\/posts\/3066\/revisions\/3377"}],"wp:attachment":[{"href":"https:\/\/www.nuvr.cz\/en\/wp-json\/wp\/v2\/media?parent=3066"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.nuvr.cz\/en\/wp-json\/wp\/v2\/categories?post=3066"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.nuvr.cz\/en\/wp-json\/wp\/v2\/tags?post=3066"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}Research of primary tumour cells<\/b><\/h4>\n
Proof-of-concept preclinical studies<\/b><\/h4>\n
Early stages of clinical studies<\/b><\/h4>\n
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