Cancer stem cells (CSCs) drive therapeutic resistance and tumor relapse by exploiting redundant regulatory networks that integrate Wnt/β-catenin, Notch, and Hedgehog signaling with metabolic reprogramming, epigenetic plasticity, and tumor microenvironment crosstalk, a network architecture that renders single-pathway inhibition strategies insufficient. This review systematically examines evidence that natural compounds (curcumin, sulforaphane, resveratrol, EGCG, berberine, and quercetin) act as multitarget modulators of CSC plasticity, analyzing their molecular mechanisms of action in specific cancer models. Each compound engages distinct regulatory nodes: curcumin suppresses β-catenin nuclear translocation and STAT3 phosphorylation in lung cancer CSC models; sulforaphane represses ΔNp63α-driven stemness transcription in colorectal cancer and reduces CSC self-renewal in prostate and head and neck models; resveratrol dissociates the β-catenin–GLI-1 interaction in oral and lung CSC populations and induces Wnt/β-catenin-dependent autophagy in breast CSCs; EGCG inhibits DNMT and HDAC activity in glioblastoma and colorectal models; berberine activates AMPK-mediated suppression of mTORC1 in colorectal cancer; and quercetin suppresses PI3K/AKT/mTOR signaling while downregulating EMT transcription factors in breast and colorectal systems. We critically assess persistent methodological limitations, including bulk cell-line models, supraphysiological concentrations, and the absence of functional tumor-initiating validation, that currently prevent stronger translational conclusions. Natural compounds from Latin American biodiversity are identified as an underexplored source of CSC-active molecules. We conclude by defining the experimental standards required to reposition natural compounds as clinically relevant network-level modulators of CSC plasticity.

Resumen— Introducción: La prescripción suplementaria (PS) por profesionales no médicos es una estrategia global para mejorar la accesibilidad y continuidad asistencial, aunque su implementación varía según marcos regulatorios locales. Objetivo: Identificar y describir las competencias y condiciones habilitantes para la prescripción suplementaria en Kinesiología en Chile, y compararlas con los marcos regulatorios y formativos internacionales reportados entre 2000 y 2025. Métodos: Revisión de alcance (PRISMA-ScR) en PubMed, Scopus, Web of Science, ERIC, SciELO y Google Scholar (2000–2025), incluyendo literatura gris. Se analizaron documentos sobre competencias, regulación y seguridad en español, inglés y portugués. Resultados: Se incluyeron 46 documentos (27 de Chile, 19 internacionales). Mientras los modelos de Reino Unido, Australia, Canadá y Brasil convergen en formación posgradual acreditada, regulación explícita y sistemas de farmacovigilancia, en Chile la normativa vigente no habilita la PS. Los programas formativos chilenos mostraron cobertura limitada en dominios críticos como gestión clínica del medicamento (37,0 %) y legislación sanitaria (0,0 %). Conclusiones: Existe una brecha significativa entre la formación de pregrado en Chile y los estándares internacionales para la PS. La implementación segura requiere desarrollar marcos regulatorios específicos y programas de capacitación avanzada. HISTORIAL DEL ARTÍCULO Fecha de recepción: 13 de octubre de 2025Fecha de aceptación: 30 de enero de 2026REFERENCIAS World Health Organization. Global strategy on human resources for health: Workforce 2030. Geneva: WHO; 2016. Disponible en: https://www.who.int/publications/i/item/9789241511131 (acceso 15 oct 2025). 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Disponible en: https://www.rpharms.com/resources/frameworks/prescribing-competency-framework/competency-framework (acceso 15 oct 2025). Chartered Society of Physiotherapy (CSP). Practice guidance for physiotherapist supplementary and/or independent prescribers: safe use of medicines. 4th ed. London: CSP; 2021. Disponible en: https://www.csp.org.uk/publications/practice-guidance-physiotherapist-supplementary-andor-independent-prescribers-safe-use (acceso 15 oct 2025). World Health Organization. Framework for action on interprofessional education & collaborative practice. Geneva: WHO; 2010. Disponible en: https://www.who.int/publications/i/item/framework-for-action-on-interprofessional-education-collaborative-practice (acceso 15 oct 2025). World Health Organization. Health system capacity for noncommunicable diseases: a global assessment. Geneva: WHO; 2020. 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Tricco AC, Lillie E, Zarin W, O’Brien KK, Colquhoun H, Levac D, et al. PRISMA Extension for Scoping Reviews (PRISMA-ScR): Checklist and Explanation. Ann Intern Med. 2018;169(7):467–473. doi:10.7326/M18-0850. Riegler TF, Marcin T,...