Identifying Druggable Therapeutic Targets for Cancer Treatment Initiatives and Adaptive Resistance

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Background

Despite the advances made during the past decades, our knowledge of resistance mechanisms remains limited in most cancer treatments. Updating the existing targets, identifying novel targets, and repurposing regimens will provide the opportunity to overcome adaptive resistance by altering downstream signalling pathways. Current mechanisms underlying drug resistance are mainly attributed to stromal effects, genomic alteration, functional adaptation of cancer cells, and heterogeneity of cancer cells themselves. Because of the multifactorial nature of drug resistance and the high cost of clinical trials of novel drugs, many challenges arise for translational research to identify new, effective therapeutic targets that can be applied for the treatment of cancer with adaptive resistance.

Identifying and determining the druggability of potential targets using functional, structural, and bioinformatics tools offers an efficient state-of-the-art strategy to find candidates to treat cancer during initiation and development of resistance.

The goal of this Research Topic is to broadly seek solutions to increase likelihood of therapeutic responses and reduce drug resistance associated with adaptive-evasive responses. Any studies addressing the prediction of the therapeutic potential of novel targets, modification of undruggable cancer drivers (either tumour promoter or suppressor), or investigating the mechanisms underlying resistance including tumour heterogeneity, immune responses, and stromal effects from tumour microenvironment are welcomed for submission. Original Research articles addressing drug discovery in relation to protein/pathways druggability, RNA and small molecule functional studies including high throughput screening, pre-clinical investigations with bioinformatic approaches, and other translational studies on novel therapeutic approaches are encouraged. Review articles aiming to understand mechanisms and summarize the current techniques to overcome drug resistance, define novel targets and/or determine druggability are also welcomed.

Areas to be covered may include, but are not limited to:
• Target druggability identification using high-throughput screening of small-molecule or genomic libraries as well as validation of novel targets for drug development.
• Validation of targeted therapies integrated with bioinformatic studies
• RNA target or structurally modified undruggable protein targets in cancer models with chemoresistance
• Mechanism behind drug resistance in all cancer types
• Single-cell level study of the heterogeneity of cancer cells showing drug-resistance
• Contribution of immune responses and tumour microenvironment to the development of drug resistance

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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