Translational Application of Circulating DNA in Oncology: Review of the Last Decades Achievements

Tuaeva, N. O.; Falzone, Luca; Porozov, Yuri; Nosyrev, Alexander E.; Трухан, В. М.; Kovatsi, Leda; Spandidos, Demetrios A.; Drakoulis, Nikolaos; Kalogeraki, Alexandra; Mamoulakis, Charalampos; Tzanakakis, George N.; Libra, Massimo; Tsatsakis, Aristidis

doi:10.3390/cells8101251

Cited by 62 publications

(49 citation statements)

References 237 publications

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“…Although there are reports suggesting a relationship between the MMR mechanism and miRNA profiles [41,43,44,46], the underlying molecular mechanism by which tobacco smoke carcinogens induce miRNA deregulation and affect the expression profiles of mismatch repair genes, particularly in lung and head and neck cancer, is not yet known.Here, we attempt to explore whether NNK affects the expression of small regulatory molecules, such as known miRNA markers, previously associated with upper aerodigestive tract malignancies [47][48][49][50][51][52][53][54] that may directly or indirectly be involved in the regulation for MMR expression phenotypes. Understanding the molecular changes induced by various risk factors, such as tobacco smoke, which promote the development and progression of cancer, will help to develop new diagnostic and therapeutic approaches [55,56], leading to optimization of their management.…”

mentioning

confidence: 99%

“…Here, we attempt to explore whether NNK affects the expression of small regulatory molecules, such as known miRNA markers, previously associated with upper aerodigestive tract malignancies [47][48][49][50][51][52][53][54] that may directly or indirectly be involved in the regulation for MMR expression phenotypes. Understanding the molecular changes induced by various risk factors, such as tobacco smoke, which promote the development and progression of cancer, will help to develop new diagnostic and therapeutic approaches [55,56], leading to optimization of their management.…”

mentioning

confidence: 99%

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The Effect of NNK, A Tobacco Smoke Carcinogen, on the miRNA and Mismatch DNA Repair Expression Profiles in Lung and Head and Neck Squamous Cancer Cells

Doukas

Vageli²,

Lazopoulos

et al. 2020

Cells

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Tobacco smoking is a common risk factor for lung cancer and head and neck cancer. Molecular changes such as deregulation of miRNA expression have been linked to tobacco smoking in both types of cancer. Dysfunction of the Mismatch DNA repair (MMR) mechanism has also been associated with a poor prognosis of these cancers, while a cross-talk between specific miRNAs and MMR genes has been previously proposed. We hypothesized that exposure of lung and head and neck squamous cancer cells (NCI and FaDu, respectively) to tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is capable of altering the expression of MSH2 and MLH1, key MMR components, by promoting specific miRNA deregulation. We found that either a low (1 µM) or high (2 µM) dose of NNK induced significant upregulation of "oncomirs" miR-21 and miR-155 and downregulation of "tumor suppressor" miR-422a, as well as the reduction of MMR protein and mRNA expression, in NCI and FaDu, compared to controls. Inhibition of miR-21 restored the NNK-induced reduced MSH2 phenotype in both NCI and FaDu, indicating that miR-21 might contribute to MSH2 regulation. Finally, NNK exposure increased NCI and FaDu survival, promoting cancer cell progression. We provide novel findings that deregulated miR-21, miR-155, and miR-422a and MMR gene expression patterns may be valuable biomarkers for lung and head and neck squamous cell cancer progression in smokers.Cells 2020, 9, 1031 2 of 22 and neck squamous cell carcinoma (HNSCC), represents one of the most aggressive malignancies with a high rate of mortality. [8,9]. Tobacco smoking has been one of the most well-established risk factors for both lung and head and neck cancers [1][2][3][4][5][6][7][8]. It is known that tobacco smoke contains a mixture of thousands of compounds, including a large number of known carcinogens [2]. It is believed that exposure of cells to tobacco smoke carcinogens can lead to DNA damage, which may cause chromosomal instability and increased cell proliferation [10][11][12][13]. In particular, tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), which is one of the chemicals in tobacco smoke, has been linked to lung and head and neck cancer [14], and has also been shown to upregulate oncogenic pathways [15][16][17].The development and progression of lung and head and neck malignancies appear to be a complex process. Although multiple diagnostic and prognostic markers have been identified for both lung and head and neck cancers [18,19], the precise molecular mechanisms involved in the development and progression of these malignancies remain unclear.We understand that a functional DNA repair mechanism that includes the recognition and repair of mismatch DNA errors during DNA replication is essential in eliminating the harmful effect of several environmental risk factors, such as NNK, on the exposed cells [20][21][22][23]. A number of studies have shown that reduced expression of mismatch DNA repair (MMR) genes increases the incidence of microsatellite ...

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confidence: 99%

mentioning

confidence: 99%

The Effect of NNK, A Tobacco Smoke Carcinogen, on the miRNA and Mismatch DNA Repair Expression Profiles in Lung and Head and Neck Squamous Cancer Cells

Doukas

Vageli²,

Lazopoulos

et al. 2020

Cells

View full text Add to dashboard Cite

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“…A valuable biomarker links the pathophysiological state and the relevant clinical endpoint. Scientific and technological advances made in recent years have enabled multiscale, longitudinal measurements (snapshots) of human biology using various biomolecules such as RNAs (mRNA, micro-RNAs, long non-coding RNAs), DNAs, proteins, metabolites, [32,[40][41][42][47][48][49][50][51][52][53][54][55][56][57][58][59] derived from patient specimens from liquid biopsy or tissue biopsy or single-cell analyses to whole-body monitoring [44,60] and that these advances have led to an increasing number of biomarkers for which targeted drugs are being discovered. Collectively, the integration of a variety of molecular profiling of patient specimens with deep, longitudinal profiling of the physiological state of an individual (i.e.…”

Section: The Usual Suspectsmentioning

confidence: 99%

Lost in translation: the valley of death across preclinical and clinical divide – identification of problems and overcoming obstacles

2019

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A rift that has opened up between basic research (bench) and clinical research and patients (bed) who need their new treatments, diagnostics and prevention, and this rift is widening and getting deeper. The crisis involving the "translation" of basic scientific findings in a laboratory setting into human applications and potential treatments or biomarkers for a disease is widely recognized both in academia and industry. Despite the attempts that have been made both in academic and industry settings to mitigate this problem, the high attrition rates of drug development and the problem with reproducibility and translatability of preclinical findings to human applications remain a fact and the return on the investment has been limited in terms of clinical impact. Here I provide an overview of the challenges facing the drug development, and translational discordance with specific focus on a number of "culprits" in translational research including poor hypothesis, irreproducible data, ambiguous preclinical models, statistical errors, the influence of organizational structures, lack of incentives in the academic setting, governmental funding mechanisms, the clinical relevance of basic research, insufficient transparency, and lack of data sharing in research. I further provide some suggestions and new strategies that include some new aspects on open innovation models, entrepreneurship, transparency, and decision making to overcome each of the many problems during the drug discovery and development process and to more dynamically adjust for innovation challenges with broader scientific feedback.

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“…Blood circulating biomarkers for detecting early pancreatic cancers have been discovered including circulating tumor DNA [111,112], exome-derived DNA [113], MicroRNA [114] (miR-93, miR-16, miR-548d-3p, etc. ), and proteins [115] (SYCN, REG1B, PRSS2, etc.).…”

Section: Application Of Blood Circulating Biomarkers For Detecting Eamentioning

confidence: 99%

Surveillance of Individuals with a Family History of Pancreatic Cancer and Inherited Cancer Syndromes: A Strategy for Detecting Early Pancreatic Cancers

et al. 2019

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A family history of pancreatic cancer (PC) is a risk factor of PC, and risk levels increase as affected families grow in number and/or develop PC at younger ages. Familial pancreatic cancer (FPC) is defined as a client having at least two PC cases in a first degree relatives. In the narrow sense, FPC does not include some inherited cancer syndromes that are known to increase the risks of PC, such as Peutz–Jeghers syndrome (PJS), hereditary pancreatitis (HP), hereditary breast ovarian cancer syndrome (HBOC), and so on. FPC accounts for 5%–10% of total PC diagnoses and is marked by several features in genetic, epidemiological, and clinicopathological findings that are similar to or distinct from conventional PC. Recent advances in genetic medicine have led to an increased ability to identify germline variants of cancer-associated genes. To date, high-risk individuals (HRIs) in many developed countries, including FPC kindreds and inherited cancer syndromes, are screened clinically to detect and treat early-stage PC. This article highlights the concept of FPC and the most recent data on its detection.

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Translational Application of Circulating DNA in Oncology: Review of the Last Decades Achievements

Cited by 62 publications

References 237 publications

The Effect of NNK, A Tobacco Smoke Carcinogen, on the miRNA and Mismatch DNA Repair Expression Profiles in Lung and Head and Neck Squamous Cancer Cells

The Effect of NNK, A Tobacco Smoke Carcinogen, on the miRNA and Mismatch DNA Repair Expression Profiles in Lung and Head and Neck Squamous Cancer Cells

Lost in translation: the valley of death across preclinical and clinical divide – identification of problems and overcoming obstacles

Surveillance of Individuals with a Family History of Pancreatic Cancer and Inherited Cancer Syndromes: A Strategy for Detecting Early Pancreatic Cancers

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