RNA interference (RNAi) is an ancient intra-cellular mechanism that regulates gene expression and cell function. Large-scale gene silencing using RNAi high-throughput screening (HTS) has opened an exciting frontier to systematically study gene function in mammalian cells. This approach enables researchers to identify gene function in a given biological context and will provide considerable novel insight. Here, we review RNAi HTS strategies and applications using case studies in cancer biology and virology.
Animals ; Genetic Predisposition to Disease ; genetics ; Humans ; Molecular Targeted Therapy ; methods ; trends ; Neoplasms ; genetics ; therapy ; RNA Interference ; Viral Proteins ; genetics ; Virus Diseases ; genetics ; therapy ; virology

RNA interference (RNAi) is a powerful endogenous process initiated by short double stranded RNAs, which results in sequence-specific posttranscriptional gene silencing. Because any protein that causes or contributes to a disease is susceptible to RNAi, the RNAi has high potential for therapeutic treatments. In a clinical setting, however, there are many obstacles to targeted delivery of small interfering RNA (siRNA) in vivo, specificity and stability of the RNAi reagents. In this review, we focus on recent progress in the development of efficient siRNA delivery vehicles to help the application of siRNA to in vivo therapy.
Drug Carriers ; Gene Transfer Techniques ; Humans ; Molecular Targeted Therapy ; methods ; trends ; RNA Interference ; RNA, Small Interfering ; administration & dosage ; genetics ; metabolism ; Transfection

Cancer is a highly aggressive and devastating disease, and impediments to a cure arise not just from cancer itself. Targeted therapies are difficult to achieve since the majority of cancers are more intricate than ever imagined. Mainstream methodologies including chemotherapy and radiotherapy as routine clinical regimens frequently fail, eventually leading to pathologies that are refractory and incurable. One major cause is the gradual to rapid repopulation of surviving cancer cells during intervals of multiple-dose administration. Novel stress-responsive molecular pathways are increasingly unmasked and show promise as emerging targets for advanced strategies that aim at both de novo and acquired resistance. We highlight recent data reporting that treatments particularly those genotoxic can induce highly conserved damage responses in non-cancerous constituents of the tumor microenvironment (TMEN). Master regulators, including but not limited to NF-kB and C/EBP-β, are implicated and their signal cascades culminate in a robust, chronic and genome-wide secretory program, forming an activated TMEN that releases a myriad of soluble factors. The damage-elicited but essentially off target and cell non-autonomous secretory phenotype of host stroma causes adverse consequences, among which is acquired resistance of cancer cells. Harnessing signals arising from the TMEN, a pathophysiological niche frequently damaged by medical interventions, has the potential to promote overall efficacy and improve clinical outcomes provided that appropriate actions are ingeniously integrated into contemporary therapies. Thereby, anticancer regimens should be well tuned to establish an innovative clinical avenue, and such advancement will allow future oncological treatments to be more specific, accurate, thorough and personalized.
Antineoplastic Agents ; therapeutic use ; CCAAT-Enhancer-Binding Protein-beta ; metabolism ; Humans ; Models, Biological ; Molecular Targeted Therapy ; methods ; trends ; NF-kappa B ; metabolism ; Neoplasms ; drug therapy ; metabolism ; Precision Medicine ; methods ; trends ; Signal Transduction ; drug effects ; Tumor Microenvironment ; drug effects

After the approval and introduction of mirabegron, tadalafil, and botulinum toxin A for treatment of lower urinary tract symptoms/overactive bladder, focus of interest has been on their place in therapy versus the previous gold standard, antimuscarinics. However, since these agents also have limitations there has been increasing interest in what is coming next - what is in the pipeline? Despite progress in our knowledge of different factors involved in both peripheral and central modulation of lower urinary tract dysfunction, there are few innovations in the pipe-line. Most developments concern modifications of existing principles (antimuscarinics, beta3-receptor agonists, botulinum toxin A). However, there are several new and old targets/drugs of potential interest for further development, such as the purinergic and cannabinoid systems and the different members of the transient receptor potential channel family. However, even if there seems to be good rationale for further development of these principles, further exploration of their involvement in lower urinary tract function/dysfunction is necessary.
Adrenergic beta-3 Receptor Agonists/therapeutic use ; Botulinum Toxins, Type A/therapeutic use ; Drug Therapy, Combination ; Humans ; Molecular Targeted Therapy/methods/trends ; Muscarinic Antagonists/therapeutic use ; Neuromuscular Agents/therapeutic use ; Urinary Bladder, Overactive/*drug therapy