Risk-Benefit Events Associated with the Use of Aspirin for Primary Prevention of Cardiovascular Disorders

Aspirin had been introduced as a nonsteroidal anti-inflammatory molecule. As further research on aspirin started, other therapeutic effects have been revealed. Now, this molecule has become the polychrest in medical science. Aspirin has served as a drug of choice for the primary prevention of cardiovascular disease (CVD) for the last few decades. However, recent trials have raised questions on the use of aspirin for CVD prevention due to some life-threatening adverse drug events. In spite of that, outcomes of trials will surely assist to frame a guideline for anoxic administration regimen of aspirin in order to prevent CVD.

Salicylic Acid Sans Aspirin in Animals and Man

Analyses in non-aspirin takers finding salicylic acid (SA) and hydroxylated metabolites in serum also SA and salicyluric acid (SU) in urine led to a re-evaluation of dietary sources of salicylates. Fruit and vegetable sources explained higher levels found in drug-free vegetarians, which overlapped with those from patients on low dose aspirin. That drug’s chemo-protective action in cancer is, at least partially, attributable to its principal metabolite, SA—which we believe contributes to the benefits of a vegetarian diet. However, diet is unlikely to be the sole source of the circulating salicylate found in aspirin-free animals and man. We adduced evidence for its persistence in prolonged fasting and biosynthesis in vivo from labelled benzoic acid. We review the roles, defined and potential, of SA in the biosphere. Emphasis on the antiplatelet effect of aspirin in man has detracted from the likely pivotal role of SA in many potential areas of bioregulation—probably as important in animals as in plants. In this expanding field, some aspirin effects, mediated by apparently conserved receptors responding to SA, are discussed. The perspectives revealed may lead to re-evaluation of the place of salicylates in therapeutics and potentially improve formulations and drug delivery systems.

Repurposing Infectious Pathogen Vaccines in Cancer Immunotherapy

Reports in the literature show that certain vaccines against infectious pathogens, can be effective in eliciting antitumor immune response when injected intratumorally. In mouse tumor models, intratumoral delivery of rotavirus, yellow fever, and influenza vaccines have been shown to also synergize with checkpoint inhibitors, in the leading immunotherapy in the clinical practice today. The combined approach can thus become a very promising novel strategy for anticancer immunotherapy. In humans, an attenuated poliomyelitis virus vaccine, a peptide-based vaccines against papilloma and one based on detoxified diphtheria protein have already been tested as intratumoral treatments readily. In those studies, the role of available anti-pathogen immunity appears an important element in mediating the activity of the repurposed vaccines against cancer. We therefore suggest how evaluating or eventually developing anti-pathogen immunity before intratumoral delivery could be helpful in repurposing infectious pathogen vaccines in cancer immunotherapy.

Drug Repositioning for the Treatment of Glioma: Current State and Future Perspective

Gliomas are the most common primary brain tumors. Among them, glioblastoma (GBM) possesses the most malignant phenotype. Despite the current standard therapy using an alkylating anticancer agent, temozolomide, most patients with GBM die within 2 years. Novel chemotherapeutic agents are urgently needed to improve the prognosis of GBM. One of the solutions, drug repositioning, which broadens the indications of existing drugs, has gained attention. Herein, we categorize candidate agents, which are newly identified as therapeutic drugs for malignant glioma into 10 classifications based on these original identifications. Some drugs are in clinical trials with hope. Additionally, the obstacles, which should be overcome in order to accomplish drug repositioning as an application for GBM and the future perspectives, have been discussed.

Drug Repurposing (DR): An Emerging Approach in Drug Discovery

Drug repurposing (DR) (also known as drug repositioning) is a process of identifying new therapeutic use(s) for old/existing/available drugs. It is an effective strategy in discovering or developing drug molecules with new pharmacological/therapeutic indications. In recent years, many pharmaceutical companies are developing new drugs with the discovery of novel biological targets by applying the drug repositioning strategy in drug discovery and development program. This strategy is highly efficient, time saving, low-cost and minimum risk of failure. It maximizes the therapeutic value of a drug and consequently increases the success rate. Thus, drug repositioning is an effective alternative approach to traditional drug discovery process. Finding new molecular entities (NME) by traditional or de novo approach of drug discovery is a lengthy, time consuming and expensive venture. Drug repositioning utilizes the combined efforts of activity-based or experimental and in silico-based or computational approaches to develop/identify the new uses of drug molecules on a rational basis. It is, therefore, believed to be an emerging strategy where existing medicines, having already been tested safe in humans, are redirected based on a valid target molecule to combat particularly, rare, difficult-to-treat diseases and neglected diseases.

Drug Repurposing in Neurological Diseases: Opportunities and Challenges

Drug repurposing or repositioning refers to “studying of clinically approved drugs in one disease to see if they have therapeutic value and do not trigger side effects in other diseases.” Nowadays, it is a vital drug discovery approach to explore new therapeutic benefits of existing drugs or drug candidates in various human diseases including neurological disorders. This approach overcomes the shortage faced during traditional drug development in grounds of financial support and timeline. It is especially hopeful in some refractory diseases including neurological diseases. The feature that structure complexity of the nervous system and influence of blood–brain barrier permeability often becomes more difficult to develop new drugs in neuropathological conditions than diseases in other organs; therefore, drug repurposing is particularly of utmost importance. In this chapter, we discuss the role of drug repurposing in neurological diseases and make a summarization of repurposing candidates currently in clinical trials for neurological diseases and potential mechanisms as well as preliminary results. Subsequently we also outline drug repurposing approaches and limitations and challenges in the future investigations.

Drugs Repurposing for Multi-Drug Resistant Bacterial Infections

Different institutions recognized that antimicrobial resistance is a global health threat that has compounded by the reduction in the discovery and development of new antimicrobial agents. Therefore, the development of new antimicrobial therapeutic strategies requires immediate attention to avoid the 10 million deaths predicted to occur by 2050 as a result of multidrug-resistant (MDR) bacteria. Despite the great interest in the development of repurposing drugs, only few repurposing drugs are under clinical development against Gram-negative critical-priority pathogens. In this chapter, we aim: (i) to discuss the therapeutic potential of the repurposing drugs for treating MDR bacterial infections, (ii) to summarize their mechanism of action, and (iii) to provide an overview for their preclinical and clinical development against these critical-priority pathogens.

Repurposing Fumaric Acid Esters to Treat Conditions of Oxidative Stress and Inflammation: A Promising Emerging Approach with Broad Potential

The medicinal benefit of salts of fumaric acid and its esters (FAE), known as fumarates (mono and dimethyl fumarate), was realized many years ago. Early on, FAE were derived from plants and mushrooms (e.g., Fumaria officinalis, Boletus fomentarius var. pseudo-igniarius). The FAE containing formulation Fumaderm® was licensed in Germany for the treatment of psoriasis in 1994. Recently, a clinical formulation of dimethyl fumarate known as BG12 (Tecfidera) was approved for use in the United States, New Zealand, Australia, European Union, Switzerland, and Canada for the treatment of multiple sclerosis. Others and we have assessed the potential benefit of FAE in a number of disease conditions that are diverse with respect to etiology but unified with regard to the involvement of inflammation and oxidative stress. Hence, a FAE-based drug with robust anti-oxidative and anti-inflammatory effects that is already US-FDA approved is a perfect contender for repurposing and rapid clinical implementation for their management. There is a burgeoning literature on the use of FAE in the prevention and treatment of diseases, other than psoriasis and MS, in which oxidative stress and/or inflammation are prominent. This chapter highlights critical information gleaned from these studies, exposes lacunae of potential importance, and provides related perspectives.

Drug Repurposing in Oncotherapeutics

Repurposing or repositioning means validating and application of previously approved drugs in the treatment of another disease that might be relevant or irrelevant to existing use in disease based on the principle of polypharmacology. Repurposed drugs are already well documented for pharmacokinetic, pharmacodynamic, drug interaction, and toxicity parameters. In 1962, thalidomide treatment in pregnant women led to phocomelia in their newborn but while repurposed based on anti-angiogenesis property, it showed efficacy in hematologic malignancies like multiple myeloma. The repurposing is becoming an essential tool in the anti-cancer drug development due to existing drugs are not effective, high cost of treatment, therapy may degrade the quality of life, improvement of survival after treatment is not guaranteed, relapse may occur, and drug resistance may develop due to tumor heterogeneity. Repurposing can be addressed well with the help of literature-based discovery, high throughput technology, bioinformatics multi-omics approaches, side effects, and phenotypes. Many regulatory bodies like EML, NIH, and FDA promote repurposing programs that support the identification of alternative uses of existing medicines. Cancer becomes the major health issue, and the need to discover promising anti-cancer drugs through repurposing remains very high due to decline in FDA approval since 1990, huge expenses incurred in the drug development and prediction of dangerous future burden.

Drug Repurposing in Dermatology: Molecular Biology and Omics Approach

The withdrawal of several blockbuster drugs due to severe adverse effects and the failure of several developed drugs in clinical trials raised questions about the efficacy of current approaches of drug discovery. Moreover, the limitation of resources and the long and costive process of drug discovery made a lot of pharmaceutical companies to employ drug repurposing strategies to get new insights about activities that were not considered during their initial discovery. The development of therapeutics for treatment of dermatological condition is not considered as priority although it affects the lifestyle of thousands of people around the world. Serendipity and observations have contributed significantly in this field but immerse efforts have been exerted to find systematic methods to identify new indications for drugs, especially with the unprecedented progress in molecular biology and omics. So, in this chapter, we will emphasize on different approaches used for drug repositioning and how it was applied to find new therapeutics for different dermatoses.