Graphical abstract The etiology of the majority of human cancers is associated with a myriad of environmental causes, including physical, chemical, and biological factors. DNA damage induced by such mutagens is the initial step in the process of carcinogenesis resulting in the accumulation of mutations. Mutational events are considered the major triggers for introducing genetic and epigenetic insults such as DNA crosslinks, single- and double-strand DNA breaks, formation of DNA adducts, mismatched bases, modification in histones, DNA methylation, and microRNA alterations. However, DNA repair mechanisms are devoted to protect the DNA to ensure genetic stability, any aberrations in these calibrated mechanisms provoke cancer occurrence. Comprehensive knowledge of the type of mutagens and carcinogens and the influence of these agents in DNA damage and cancer induction is crucial to develop rational anticancer strategies. This review delineated the molecular mechanism of DNA damage and the repair pathways to provide a deep understanding of the molecular basis of mutagenicity and carcinogenicity. A relationship between DNA adduct formation and cancer incidence has also been summarized. The mechanistic basis of inflammatory response and oxidative damage triggered by mutagens in tumorigenesis has also been highlighted. We elucidated the interesting interplay between DNA damage response and immune system mechanisms. We addressed the current understanding of DNA repair targeted therapies and DNA damaging chemotherapeutic agents for cancer treatment and discussed how antiviral agents, anti-inflammatory drugs, and immunotherapeutic agents combined with traditional approaches lay the foundations for future cancer therapies.
Aim/Hypothesis: The complexity and heterogeneity of multiple pathological features make Alzheimer’s disease (AD) a major culprit to global health. Drug repurposing is an inexpensive and reliable approach to redirect the existing drugs for new indications. The current study aims to study the possibility of repurposing approved anticancer drugs for AD treatment. We proposed an in silico pipeline based on “omics” data mining that combines genomics, transcriptomics, and metabolomics studies. We aimed to validate the neuroprotective properties of repurposed drugs and to identify the possible mechanism of action of the proposed drugs in AD. Results: We generated a list of AD-related genes and then searched DrugBank database and Therapeutic Target Database to find anticancer drugs related to potential AD targets. Specifically, we researched the available approved anticancer drugs and excluded the information of investigational and experimental drugs. We developed a computational pipeline to prioritize the anticancer drugs having a close association with AD targets. From data mining, we generated a list of 2914 AD-related genes and obtained 49 potential druggable targets by functional enrichment analysis. The protein–protein interaction (PPI) studies for these genes revealed 641 interactions. We found that 15 AD risk/direct PPI genes were associated with 30 approved oncology drugs. The computational validation of candidate drug–target interactions, structural and functional analysis, investigation of related molecular mechanisms, and literature-based analysis resulted in four repurposing candidates, of which three drugs were epidermal growth factor receptor (EGFR) inhibitors. Conclusion: Our computational drug repurposing approach proposed EGFR inhibitors as potential repurposing drugs for AD. Consequently, our proposed framework could be used for drug repurposing for different indications in an economical and efficient way.
Background: The global alliance for genomics and healthcare facilities provides innovational solutions to expedite research and clinical practices for complex and incurable health conditions. Precision oncology is an emerging field explicitly tailored to facilitate cancer diagnosis, prevention and treatment based on patients’ genetic profile. Advancements in “omics” techniques, next-generation sequencing, artificial intelligence and clinical trial designs provide a platform for assessing the efficacy and safety of combination therapies and diagnostic procedures. Method: Data were collected from Pubmed and Google scholar using keywords: “Precision medicine”, “precision medicine and cancer”, “anticancer agents in precision medicine” and reviewed comprehensively. Results: Personalized therapeutics including immunotherapy, cancer vaccines, serve as a groundbreaking solution for cancer treatment. Herein, we take a measurable view of precision therapies and novel diagnostic approaches targeting cancer treatment. The contemporary applications of precision medicine have also been described along with various hurdles identified in the successful establishment of precision therapeutics. Conclusion: This review highlights the key breakthroughs related to immunotherapies, targeted anticancer agents, and target interventions related to cancer signaling mechanisms. The success story of this field in context to drug resistance, safety, patient survival and in improving quality of life is yet to be elucidated. We conclude that, in the near future, the field of individualized treatments may truly revolutionize the nature of cancer patient care.
Objectives Oxidative stress is a major cellular burden that triggers reactive oxygen species (ROS) and antioxidants that modulate signalling mechanisms. Byproducts generated from this process govern the brain pathology and functions in various neurological diseases. As oxidative stress remains the key therapeutic target in neurological disease, it is necessary to explore the multiple routes that can significantly repair the damage caused due to ROS and consequently, neurodegenerative disorders (NDDs). Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is the critical player of oxidative stress that can also be used as a therapeutic target to combat NDDs. Key findings Several antioxidants signalling pathways are found to be associated with oxidative stress and show a protective effect against stressors by increasing the release of various cytoprotective enzymes and also exert anti-inflammatory response against this oxidative damage. These pathways along with antioxidants and reactive species can be the defined targets to eliminate or reduce the harmful effects of neurological diseases. Summary Herein, we discussed the underlying mechanism and crucial role of antioxidants in therapeutics together with natural compounds as a pharmacological tool to combat the cellular deformities cascades caused due to oxidative stress
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