Questions that can be answered by biomarkers. Huntington's disease is an autosomal dominant, progressive neurodegenerative disorder, for which there is. - презентация

1 Questions that can be answered by biomarkers

2 Huntington's disease is an autosomal dominant, progressive neurodegenerative disorder, for which there is no disease-modifying treatment. By use of predictive genetic testing, it is possible to identify individuals who carry the gene defect before the onset of symptoms, providing a window of opportunity for intervention aimed at preventing or delaying disease onset. However, without robust and practical measures of disease progression (ie, biomarkers), the efficacy of therapeutic interventions in this premanifest Huntington's disease population cannot be readily assessed. Current progress in the development of biomarkers might enable evaluation of disease progression in individuals at the premanifest stage of the disease; these biomarkers could be useful in defining endpoints in clinical trials in this population. Clinical, cognitive, neuroimaging, and biochemical biomarkers are being investigated for their potential in clinical use and their value in the development of future treatments for patients with Huntington's disease. To read this article in full you will need to make a payment

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4 Representation of the diagnostic, prognostic, and predictive uses of circulating miRNAs as a biomarker using lung cancer as an example.

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6 As shown in the image is considered that the loss of function of the APC protein is one of the mutations that determine the tissue hyperplasia that leads to the development of the early adenoma. Additional mutations, particularly those that cause hyperactivation of KRAS protein and inactivation of various tumor suppressor genes (including p53) are responsible for the subsequent progression of the tumor. Of particular importance to understand the current treatments and issues related to them is KRAS pathway. This pathway is physiologically present in all cells capable of replication (such as stem cells) and is essential for the proliferation and cell survival.

7 In recent years, the clinical development of targeted therapies has been advanced by a greater understanding of tumor biology and genomics. Nonetheless, drug development remains a slow and costly process. An additional challenge is that targeted therapies may benefit only a subset of patients treatedtypically those patients whose tumors are dependent on the target of interest. Thus, there is a growing need for the incorporation of both predictive and pharmacodynamic (PD) biomarkers in drug development. Predictive biomarkers are important to help guide patient selection, while PD biomarkers can provide information on the pharmacologic effects of a drug on its target. PD studies may provide insights into proof of mechanism (i.e., Does the agent hit its intended target?) and proof of concept (i.e., Does hitting the drug target result in the desired biologic effect?). PD studies may also provide information on the optimal biologic dosing or scheduling of a targeted agent. Herein, we review PD endpoints in the context of targeted drug development in non–small cell lung cancer, highlighting some of the key challenges encountered to date. In doing so, we discuss recent experiences with repeat tumor biopsies, surrogate tissue analysis, alternative clinical trial designs (e.g., window-of-opportunity trials), circulating biomarkers, and mechanism-based toxicity assessments. The application of such technologies and biomarkers in early clinical trials may facilitate rational drug development, while enhancing our understanding of why certain targeted therapies succeed or fail.

8 Genomic technologies used to uncover biomarkers for colorectal cancer molecular classification, diagnosis, prognosis, surveillance and therapy response. CGH, comparative genomic hybridisation; CNVs, copy number variations; SVs, structural variations; SNPs, single nucleotide polymorphisms; qRT-PCR, quantitative real-time PCR;

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10 Potential biomarker and therapeutic applications of N- glycans. Serum N-glycan profiling (e.g., via mass

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