Expert opinion on therapeutic targets
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Expert Opin. Ther. Targets · May 2013
ReviewMicroRNAs: promising therapeutic targets for the treatment of pulmonary arterial hypertension.
MicroRNAs (miRNAs) are small noncoding RNAs that not only regulate gene expression during normal development but can also be active players in several diseases. To date, several studies have demonstrated a possible role for specific miRNAs in the regulation of pulmonary vascular homeostasis suggesting that novel therapeutic agents which target these modulators of gene expression could serve to treat pulmonary arterial hypertension (PAH). ⋯ Further understanding of miRNA biology and function in the pulmonary circulation will serve to further enhance our understanding of their contribution to the pathogenesis of PAH. The implementation of a systems biology approach will help accelerate the discovery of miRNAs that influence angiogenesis and cellular responses to vascular injury. Experimental characterization of these miRNAs using in vitro and in vivo methods will be required to validate the biological roles of these miRNAs prior to the consideration of their use as therapeutic targets in future clinical trials.
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Epigenetic changes have been detected in thyroid cancer cells, and evidence indicates that they may contribute to altered differentiation and proliferation of these cells. Histone acetylation/deacetylation represents a major mechanism for modulating the expression of genes, including those involved in neoplastic transformation, and drugs that inhibit histone deacetylase (HDAC) activity have displayed promising anti-tumor activity in many pre-clinical studies. ⋯ HDACs are a potentially important target for thyroid cancer treatments. Inhibition of HDAC activity has produced encouraging results in terms of reducing proliferation rates and restoring the iodine-uptake capacity in transformed thyrocytes. HDACi, especially when combined with other molecularly targeted drugs, may represent an important option for those tumors that are unresponsive to the currently available treatments.
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Fibromyalgia is a debilitating, chronic pain disorder typically present with allodynia and hyperalgesia. Estimates from the USA suggest that fibromyalgia affects about 5% of women, and is the third most common rheumatic disorder after lower back pain and osteoarthritis. Recent research advances highlighted a role for aberrant central pain processing in fibromyalgia, and consistent with this, the first three drugs (pregabalin, duloxetine and milnacipran) approved by the FDA for fibromyalgia over the past 2 years have a predominantly central mode of action. Despite progress in understanding of fibromyalgia and the long-awaited introduction of three medications for treating it, fibromyalgia continues to pose a significantly unmet medical need, negatively affecting the lives of millions of individuals worldwide in all ethnic groups and all economic classes. ⋯ Current research on novel sedative-hypnotics, anti-epileptic medications, various reuptake inhibitors, growth hormone agonists, canabinoid agonists, non-opiate analgesics and 5-HT3 antagonists offers hope for the the next generation of therapeutic options for fibromyalgia. With regards to the development of novel pharmacotherapies, there seem to be grounds for increased optimism regarding prospective treatments of the disorder.
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Expert Opin. Ther. Targets · Sep 2011
ReviewThe role of inflammation in the pathogenesis of lung cancer.
It is reported that cancer may arise in chronically inflamed tissue. There is mounting evidence suggesting that the connection between inflammation and lung cancer is not coincidental but may indeed be causal. The inflammatory molecules may be responsible for augmented macrophage recruitment, delayed neutrophil clearance and an increase in reactive oxygen species. The cytokines and growth factors unusually produced in chronic pulmonary disorders have been found to have harmful properties that pave the way for epithelial-to-mesenchymal transition and tumor microenvironment. However, the role of inflammation in lung cancer is not yet fully understood. ⋯ Advances in tumor immunology support the clinical implementation of immunotherapies for lung cancer. Along with therapeutic benefits, immunotherapy presents the challenges of drug-related toxicities. Gene modification of immunocytokine may lower the associated toxic effects.
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Expert Opin. Ther. Targets · May 2011
ReviewMicroRNAs in adipogenesis and as therapeutic targets for obesity.
Obesity and obesity-related disease have reached pandemic proportions and are prevalent even in developing countries. Adipose tissue is increasingly being recognized as a key regulator of whole-body energy homeostasis and consequently as a prime therapeutic target for metabolic syndrome. This review discusses the roles of miRNAs, small endogenously expressed RNAs that regulate gene expression at a post-transcriptional level, in the development and function of adipose tissue and other relevant metabolic tissues impacted by obesity. Several high-throughput studies have identified hundreds of miRNAs that are differentially expressed during the development of metabolic tissues or as an indication of pathophysiology. Further investigation has functionalized the regulatory capacity of individual miRNAs and revealed putative targets for these miRNAs. Therefore, as with several other pathologies, miRNAs are emerging as feasible therapeutic targets for metabolic syndrome. ⋯ miRNAs are extensive regulators of adipocyte development and function and are viable therapeutic targets for obesity. Despite the broad-spectrum and redundancy of miRNA-target interactions, sophisticated bioinformatic approaches are making it possible to determine the most physiologically relevant miRNAs to target in disease. In vivo delivery of miRNAs for therapeutic purposes is rapidly developing and has been successful in other contexts. Additionally, miRNAs can be used as prognosis markers for disease onset and progression. Ultimately, miRNAs are prime therapeutic targets for obesity and its consequent pathologies in other metabolic tissues.