Elucidating mechanisms

24-Mar-2020 05:43 by 2 Comments

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An important part of MCA′s strategy is to conduct research to develop genomic and epigenomic methodologies, profiling strategies, and bioinformatics tools and resources that are applicable to biobanks associated with population-based studies.MCA also contributes to the development of translational studies, through the discovery of mechanism-based biomarkers of exposure and cancer risk, and to cancer research that is relevant, although not exclusive, to low- and middle-income countries (LMICs).

With the opportunities provided by these advances in mind, MCA′s strategy will focus on two priority areas.

MCA participates in an interdisciplinary approach aimed at characterizing exposures throughout the life-course (with a particular focus on the fetal exposome and childhood cancer) by building upon advances in laboratory science (“omics” technologies) and unique samples from international population-based cohorts (collaboration with IARC Groups: Genetic Cancer Susceptibility (GCS), Biomarkers (BMA), Infections and Cancer Biology (ICB), and Biostatistics (BST)).

Identification of epigenetic signatures linked to measures of environmental exposures throughout life (the exposome) should facilitate the development of (epi)genome-based biomarkers of cancer risk and mechanism-based biomarkers of exposures.

Therefore, the development of epigenomic and profiling strategies, as well as bioinformatics tools, applicable to population-based cohorts, epidemiology, and carcinogen evaluation remains an essential part of MCA′s strategy.

Furthermore, MCA develops pipelines for (epi)genome-wide profiling and targeted (epi)genetics in high-throughput settings and robust bioinformatics analysis, all of which should facilitate identification of causal pathways linking the exposome measures and early mechanistic effects leading to cancer.

Recent developments in the Section brought about by new strategic decisions and recruitments have enabled a shift in approach, with a greater emphasis on integrated omics-level strategies and methods for studying mechanisms of carcinogenesis and biomarker discovery.

The added expertise brought about by the recruitments has enabled the development of new, multidisciplinary projects that exploit recent conceptual and technological advances.Finally, MCA will build upon whole-(epi)genome profiles released by major sequencing efforts (TCGA, IHEC) and take advantage of existing molecular epidemiology studies in LMICs and targeted (epi)genomics to develop an approach for (epi)genomic classification in order to distinguish screen-detected or early-stage lesions according to their risk of progression to an invasive process (the focus will be on breast cancer; collaboration with IARC Groups and Sections: MMB, GCS, Molecular Pathology (MPA), and Nutritional Epidemiology (NEP)).Demands for faster, more affordable, and less labour-intensive strategies are increasingly met by several emerging technologies that have demonstrated the capacity to deliver next-generation solutions for fast and cost-effective (epi)genome sequencing.In this context, MCA is well placed to enhance the evidence base for understanding the causes and prevention of cancer.The Section comprises two Groups: the Molecular Mechanisms and Biomarkers Group (MMB) and the Epigenetics Group (EGE), which work in close collaboration to create synergies and better exploit and further expand unique research tools and expertise.The Section of Mechanisms of Carcinogenesis (MCA), headed by Dr Zdenko Herceg, is responsible for studies aimed at elucidating molecular mechanisms by which environmental exposures induce genetic and epigenetic alterations and deregulate molecular pathways critical for cancer development and progression.

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