About this Research Topic

Background

The classical targets of drugs such as G-protein coupled receptors, kinases, and transporters have driven the drug development process over the past several decades. This established framework is currently being challenged by molecular targeted therapies and biologics, but one aspect of the clinical applications of all of these drugs has remained unchanged, and that is drug resistance (both de novo and acquired), especially observed in cancer patients. Alterations in a number of classical molecular mechanisms such as drug efflux, DNA damage repair, epithelial-mesenchymal transition, drug metabolism, and signalling pathways have been extensively deliberated. Mounting evidence has also linked relatively new processes such as enhanced cholesterol biosynthesis and its intracellular accumulation as a key mechanism contributing to resistance in not only cancer cells but also in cancer stem cells. Additionally, the role of non-coding RNAs cannot be ignored while attempting to understand drug resistance mechanisms at a molecular level.

The research from several different disciplines has highlighted the utility of combination therapies, nanotechnology, epigenetic drugs, etc. in reducing cancer drug resistance in in vitro and in vivo models. Cholesterol-lowering agents such as statins have recently entered several clinical trials as future treatment option for cholesterol-rich cancers such as breast cancer. Although omics technologies have identified specific molecular changes and genetic mutations associated with cancer drug resistance, challenges still remain to identify specific key targets that drive cancer drug resistance and can be potential targets of developing drugs in the future to regulate drug resistance pathways in cancer cells. New drug combinations can be developed to counteract resistance associated with long-term usage of clinical drugs. The role of non-coding RNAs such as miRNA is not well explored in modulating drug response in cancer cells and offers an exciting area of research to delineate unknown participating pathways.

This Research Topic is dedicated to publishing research focusing on exploring different aspects of cancer drug resistance, particularly less investigated areas such as the role of cholesterol accumulation and non-coding RNAs in mediating drug resistance in cancer cells as well as cancer stem cells. The Topic also seeks submissions on the latest therapeutic developments in this area of research. The themes to be covered below are of particular interest but are not limited to:

• Mechanisms driving drug resistance in cancer
• Mutations imparting cancer drug resistance
• Cholesterol-mediated drug resistance in cancer
• Establishing the role of non-coding RNAs (particularly miRNAs) in cancer drug resistance
• Identification of new biomarkers to monitor development of drug resistance
• Modulation of processes such as drug efflux through ABC transporters to counteract drug resistance
• Therapeutic potential and applications of cholesterol lowering agents
• Methods to enhance sensitivity of cancer cells to clinical drugs

We welcome Review articles, Original Research (basic research or translational studies), and clinically relevant biomarkers for monitoring the therapeutic response of patients to drugs, etc.

Keywords: cancer drug resistance, cholesterol, non-coding RNA, therapeutic

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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