Current status of biomarker research in neurology

Polívka, Jiří; Krakorova, Kristyna; Peterka, Marek; Topolčan, Ondřej

doi:10.1186/s13167-016-0063-5

Cited by 36 publications

(23 citation statements)

References 154 publications

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“…Multifactorial physical and cognitive disability of NNND-affected patient cohorts results from individual interplay of genetic, epigenetic and environmental risk factors. Contextually, the comprehensive area of NNND demands new strategies which would create a robust platform for the cost-effective medicine of future NNND management [39–42]. Consequently, the advanced PPPM concepts do place particular emphasis on primary prevention by the identification of predisposed individuals, improved patient stratification and treatments tailored to the person [6].…”

Section: Predictive Preventive and Personalised Medicine (Pppm)mentioning

confidence: 99%

Medicine in the early twenty-first century: paradigm and anticipation - EPMA position paper 2016

et al. 2016

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Section: Predictive Preventive and Personalised Medicine (Pppm)mentioning

confidence: 99%

Medicine in the early twenty-first century: paradigm and anticipation - EPMA position paper 2016

et al. 2016

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“…The mutations in IDH1/2 serve also as an independent and important GBM prognostic factor (13)(14)(15). Their routine assessment is now highly recommended in the clinical management of patients with glioma (including GBM) according to the recently updated World Health Organization (WHO) 2016 classification of CNS tumors (16)(17)(18).…”

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confidence: 99%

Advances in Experimental Targeted Therapy and Immunotherapy for Patients with Glioblastoma Multiforme

Polívka

Holubec

Kubíková

et al. 2017

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Abstract. Glioblastoma multiforme (GBM) represents the most malignant primary brain tumor in adults with generally dismal prognosis, early clinical deterioration and high mortality. GBM is extremely invasive, characterized by intense and aberrant vascularization and high resistance to multimodal treatment. Standard therapy (surgery, radiotherapy and chemotherapy with temozolomide) has very limited effectiveness, with median overall survival of patients no longer than 15 months. Progress in genetics and epigenetics of GBM over the past decade has revealed various aberrations in cellular signaling pathways, the tumor microenvironment, and pathological angiogenesis. A number of targeted anticancer drugs, such as small-molecule kinase inhibitors and monoclonal antibodies, have been evaluated in clinical trials with newly-diagnosed, as well as recurrent GBM. Unfortunately, to date, only a single antiangiogenic agent, bevacizumab, has been approved for the treatment of recurrent GBM in the USA and Canada. The novel possibilities of cancer immunotherapy, especially immune checkpoint inhibitors, are being evaluated in clinical trials of patients with GBM. The most recent clinical experiences with targeted therapy as well as immunotherapy of GBM are given in this review. The relative lack of success of some of these approaches recently revealed in well-designed randomized clinical trials is also discussed.Glioblastoma multiforme (GBM) belongs to the largest group of primary central nervous system (CNS) tumors, so-called gliomas, which are formed from supporting glial cells in the brain parenchyma (1, 2). GBM represents the most common and most malignant tumor in this class, with an incidence of 3-4/100,000/year (3, 4). GBM is an extremely invasive and difficult to treat tumor, characterized by intense and aberrant vascularization and high resistance to radiotherapy (RT) and chemotherapy (CHT). The current standard of care for patients with newly-diagnosed GBM comprises of neurosurgery and subsequent concomitant chemoradiotherapy by fractionated external-beam RT and systemic temozolomide followed by systemic temozolomide in the adjuvant setting (5). There are only very limited possibilities for the treatment of subsequent recurrences, generally with minimal clinical efficacy (6). Despite intensive multimodal treatment strategies, the median survival of patients with GBM is still 12.1-14.6 months and only 3-5% of patients survive longer than 3 years (7).Enormous progress has been made in the genetics and epigenetics of GBM during the past decade. The Cancer 21Τhis article is freely accessible online.Correspondence to: Jiri Polivka, Department of Neurology, Faculty Hospital Plzen, alej Svobody 80, 304 60, Plzen, Czech Republic. E-mail: polivka@fnplzen.cz Key Words: Glioblastoma multiforme, GBM, targeted therapy, immunotherapy, immune checkpoint inhibitors, PD1 inhibition, CTLA4 inhibition, clinical trials, personalized medicine, review. ANTICANCER RESEARCH 37: 21-34 (2017) [8][9][10][11][12]. The most important genetic...

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“…Identifying circulating biomarkers is of particular importance in neurological disease states in which access to diseased neural tissue in vivo is almost impossible. Furthermore, in neurodegenerative disorders, symptomatology may appear in only advanced clinical states, necessitating early detection and intervention (Polivka et al, 2016). Elucidating the factors which underpin inter-individual variation in plasma protein levels can inform disease biology and also identify proteins with likely causal roles in a given disease, augmenting their value as predictive biomarkers.…”

Section: Introductionmentioning

confidence: 99%

Genetic and epigenetic architectures of neurological protein biomarkers in the Lothian Birth Cohort 1936

Hillary¹,

McCartney²,

Harris³

et al. 2019

Preprint

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Although plasma proteins may serve as important markers of disease risk in neurological conditions, the molecular mechanisms responsible for inter-individual variation in plasma protein levels are poorly understood. In this study, we conducted genome-and epigenome-wide association studies on the levels of 92 neurological proteins to identify genetic and epigenetic loci associated with their plasma concentrations (n = 750). We identified 62 independent genome-wide significant loci for 37 proteins (P < 5.4 x 10 -10 ) and 68 epigenome-wide significant sites associated with the levels of 7 proteins (P < 3.9 x 10 -10 ). Using this information, we identified biological pathways in which putative neurological biomarkers are implicated as well as molecular mechanisms through which genetic variation may perturb plasma protein levels. Additionally, we found evidence that poliovirus receptor is causally associated with Alzheimer's disease. In conclusion, we identified many novel genetic and epigenetic factors that are associated with neurological protein levels which may inform disease biology and establish causal relationships between biomarkers and neurological diseases. Conception and design: RFH and REM. Data analysis: RFH, DLMcC, DCL and REM. Drafting the article: RFH and REM. Revision of the article: all authors.

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Current status of biomarker research in neurology

Cited by 36 publications

References 154 publications

Medicine in the early twenty-first century: paradigm and anticipation - EPMA position paper 2016

Medicine in the early twenty-first century: paradigm and anticipation - EPMA position paper 2016

Advances in Experimental Targeted Therapy and Immunotherapy for Patients with Glioblastoma Multiforme

Genetic and epigenetic architectures of neurological protein biomarkers in the Lothian Birth Cohort 1936

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