About this Research Topic
Today, cancer resistance to therapy is known to be triggered by complex and multifactorial causes, with primary or inherent resistance being exhibited by tumors prior to the first administration of the agent, and acquired resistance being shown by tumors that develop secondary unresponsiveness to therapy after an initial positive response.
One of the factors recently discovered to play a crucial role in drug resistance is the extracellular vesicle (EV)-based communication system, which links tumor cells to the surrounding and distant microenvironment.
EVs are cell-derived membrane-confined particles with different biogenesis and size range carrying a wide array of molecules, such as proteins, DNA and different classes of RNAs. EVs serve as powerful modulators of the molecular, metabolic and biochemical properties of the tumor microenvironment, with relevant consequences on the behavior and phenotype of tumor and cancer cells. In addition, over the last few years, several in vitro, in vivo and clinical studies provided evidence for a EV-mediated transmission of drug-resistance traits from cell to cell in a variety of malignancies, such as breast, prostate, lung and ovarian cancer.
With regard to the pathways activated by EVs in cancer cells undergoing adaptation to therapeutic interventions, it is worth noting that a key role is played by regulatory RNAs (namely, lncRNAs and miRNAs) and drug efflux pumps, but much more still seems to be elucidated. Moreover, exosomes are suspected to promote drug resistance by reprogramming the metabolism of cancer cells and their surrounding stromal cells, with extensive changes in mitochondrial function, bioenergetics, reactive oxygen species (ROS) production and disposal, as well as in genomic stability and epigenetic control of gene expression. In addition, the efficacy of the chimeric antigen receptor (CAR) T-based therapy, which represents a promising way to re-program T cells in vitro to find and destroy cancer cells, has been recently found to be limited by important immune escape mechanisms linked to tumor-derived extracellular vesicles.
Intriguingly, despite the increasing interest in the field of cancer resistance to therapy, the exact molecular mechanisms that are mediated by EVs in neoplasms and malignancies entering a therapy resistant condition are still largely unclear.
This research topic welcomes original researches and review articles that are focused on clarifying the mechanisms underlying EV-driven intrinsic protective traits and acquired adaptive responses observed in cancers and tumors upon physical, chemical and immune-based anti-cancer interventions.
In particular, this collection aims at elucidating at the best level the vast array of EV-mediated adaptations occurring in tumor and cancer cells that may lead to therapy resistance, in terms of transcriptional and translational regulation of genes involved in metabolic rewiring, antioxidant protection, cell cycle control, drug uptake/export, apoptotic death etc. In addition, researchers are also invited to provide data and opinions regarding strategies aimed at hijacking EV-controlled cellular communication systems, as well as the intracellular downstream pathways, with particular attention to pharmacological and nutraceutical approaches.
Potential topics include but are not strictly limited to the following:
1) In vitro, in vivo and/or human studies focused on EV-dependent regulation of cellular responses to anti-cancer interventions, with particular attention to metabolic reprogramming, DNA damage repairing capacity, regulation of mechanisms of drug uptake/export, antioxidative potential, redox homeostasis, control of cell cycle, proliferation and apoptosis;
2) In vitro, in vivo and/or human researches on the mechanisms underlying the action of synthetic and natural compounds on the release of EVs, as well as on EV-dependent downstream cellular pathways in tumor and malignant cells, with particular focus on relevant therapy-resistance aspects.
Please note: manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by validation (independent cohort or biological validation in vitro or in vivo) are out of scope for this section and will not be accepted as part of this Research Topic.
Keywords: cancer, extracellular vesicles, exosomes, resistance, adaptive response
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.