Exploring the Role of Cancer Stem Cells and Tumor-Initiating Cells in Therapy Resistance

Cancer biology has increasingly recognized cancer stem cells (CSCs) as pivotal contributors to tumor progression, metastasis, and treatment resistance. These rare yet potent cells are characterized by their self-renewal abilities and their capacity to regenerate the entire cellular makeup of tumors. Recent research has exposed critical challenges posed by CSCs, including their ability to remain quiescent and evade traditional therapeutic approaches aimed primarily at rapidly dividing cancer cells. Furthermore, CSCs are distinguished by their robust DNA repair mechanisms, high activity of drug efflux pumps, resistance to oxidative stress, and skillful modulation of anti-apoptotic pathways. Collectively, these properties enable CSCs to survive various therapies, enhance the risks of relapse, and escalate tumor aggressiveness upon resurgence.Studies have highlighted that CSCs not only resist chemotherapy, radiotherapy, and immunotherapy but can also convert non-stem cancer cells into stem-like states, reinforcing the tumor’s resilience. In addition to their intrinsic resistance mechanisms, CSCs manipulate their microenvironment, including interactions with immune cells and stromal components, to establish an immunosuppressive barrier that is challenging for current therapies to penetrate. By reorganizing metabolic processes, such as transitioning to oxidative phosphorylation (OXPHOS) and adapting to hypoxic, acidic conditions, CSCs further fortify themselves against therapeutic stressors. These sophisticated evasive tactics underscore the need for new diagnostic tools, therapeutic targets, and strategies dedicated to overcoming CSC-mediated resistance and preventing tumor recurrence.This Research Topic aims to advance our understanding of CSC-driven mechanisms underlying therapy evasion, with the objective of identifying innovative targets and refining therapeutic interventions. We encourage exploration into how CSCs regulate intrinsic survival pathways and interact with their microenvironment, as well as investigations into their metabolic reprogramming and adaptive behaviors. Studies that elaborate on strategies to specifically target or eradicate CSCs, or prevent their recruitment and support from surrounding cells, are particularly of interest.To gather further insights into the multifaceted roles of CSCs in cancer therapy resistance, we welcome articles addressing, but not limited to, the following themes:- Intrinsic molecular mechanisms of therapy resistance in CSCs- CSC-mediated modulation of the tumor microenvironment and immune evasion- Metabolic adaptations of CSCs in response to therapeutic pressures- Strategies for targeting CSCs in preclinical and clinical models- Diagnostic tools and biomarkers identifying CSC subpopulations- Interplay between CSCs and non-stem cancer cells in tumor relapse- Novel therapeutic agents or modalities counteracting CSC-driven resistance Topic editors: Rui Caetano Oliveira, Kevin Dzobo Source: https://www.frontiersin.org/research-topics/78678/exploring-the-role-of-cancer-stem-cells-and-tumor-initiating-cells-in-therapy-resistance