ABSTRACT
The conventional theory linking a single gene with a particular disease and a specific drug contributes to the dwindling success rates of traditional drug discovery. This requires a substantial shift focussing on contemporary drug design or drug repurposing, which entails linking multiple genes to diverse physiological or pathological pathways and drugs. Lately, drug repurposing, the art of discovering new/unlabelled indications for existing drugs or candidates in clinical trials, is gaining attention owing to its success rates. The rate-limiting phase of this strategy lies in target identification, which is generally driven through disease-centric and/or drug-centric approaches. The disease-centric approach is based on exploration of crucial biomolecules such as genes or proteins underlying pathological cascades of the disease of interest. Investigating these pathological interplays aids in the identification of potential drug targets that can be leveraged for novel therapeutic interventions. The drug-centric approach involves various strategies such as exploring the mechanism of adverse drug reactions that can unearth potential targets, as these untoward reactions might be considered desirable therapeutic actions in other disease conditions. Currently, artificial intelligence is an emerging robust tool that can be used to translate the aforementioned intricate biological networks to render interpretable data for extracting precise molecular targets. Integration of multiple approaches, big data analytics, and clinical corroboration are essential for successful target mining. This chapter highlights the contemporary strategies steering target identification and diverse frameworks for drug repurposing. These strategies are illustrated through case studies curated from recent drug repurposing research inclined towards neurodegenerative diseases, cancer, infections, immunological, and cardiovascular disorders.
Subject(s)
Drug Repositioning , Humans , Data Mining , Drug DiscoveryABSTRACT
The clinical management of oral cancer is often frequented with challenges that arise from relapse, recurrence, invasion and resistance towards the cornerstone chemo and radiation therapies. The recent conceptual advancement in oncology has substantiated the role of cancer stem cells (CSC) as a predominant player of these intricacies. CSC are a sub-group of tumor population with inherent adroitness to self-renew with high plasticity. During tumor evolution, the structural and functional reprogramming persuades the cancer cells to acquire stem-cell like properties, thus presenting them with higher survival abilities and treatment resistance. An appraisal on key features that govern the stemness is of prime importance to confront the current challenges encountered in oral cancer. The nurturing niche of CSC for maintaining its stemness characteristics is thought to be modulated by complex multi-layered components encompassing neoplastic cells, extracellular matrix, acellular components, circulatory vessels, various cascading signaling molecules and stromal cells. This review focuses on recapitulating both intrinsic and extrinsic mechanisms that impart the stemness. There are contemplating evidences that demonstrate the role of transcription factors (TF) in sustaining the neoplastic stem cell's pluripotency and plasticity alongside the miRNA in regulation of crucial genes involved in the transformation of normal oral mucosa to malignancy. This review illustrates the interplay between miRNA and various known TF of oral cancer such as c-Myc, SOX, STAT, NANOG and OCT in orchestrating the stemness and resistance features. Further, the cross-talks involved in tumor micro-environment inclusive of cytokines, macrophages, extra cellular matrix, angiogenesis leading pathways and influential factors of hypoxia on tumorigenesis and CSC survival have been elucidated. Finally, external factorial influence of oral microbiome gained due to the dysbiosis is also emphasized. There are growing confirmations of the possible roles of microbiomes in the progression of oral cancer. Given this, an attempt has been made to explore the potential links including EMT and signaling pathways towards resistance and stemness. This review provides a spectrum of understanding on stemness and progression of oral cancers at various regulatory levels along with their current therapeutic knowledge. These mechanisms could be exploited for future research to expand potential treatment strategies.
