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Redefining Chemoresistance: Natural Bioactives as Molecular Modulators at the Cancer-Tumor Microenvironment Interface

Claudia Reytor-González1, Emilia Jiménez-Flores1, Natalí González2

  • 1Universidad UTE, Facultad de Ciencias de la Salud Eugenio Espejo, Centro de Investigación en Salud Pública y Epidemiología Clínica (CISPEC), Quito 170527, Ecuador.

International Journal of Molecular Sciences
|August 28, 2025
PubMed

Insights

Natural compounds show promise in overcoming cancer therapeutic resistance by modulating cancer cell behavior and the tumor microenvironment. Further research is needed to integrate these bioactives into clinical practice for improved cancer treatment outcomes.

Area of Science:

  • Oncology
  • Pharmacology
  • Natural Products Chemistry

Background:

  • Therapeutic resistance is a major challenge in cancer treatment, leading to poor patient outcomes.
  • Natural bioactive compounds offer potential as adjuncts to overcome resistance by targeting multiple pathways.
  • Understanding their mechanisms and interactions within the tumor microenvironment is crucial.

Purpose of the Study:

  • To review the current evidence on natural compounds' role in influencing cancer cell behavior and the tumor microenvironment.
  • To provide a structured overview of natural compounds, organized by chemical families, for enhancing chemotherapy efficacy.
  • To highlight strategies for improving the clinical applicability of natural compounds in cancer therapy.

Main Methods:

  • Systematic review of preclinical and clinical studies on natural compounds and cancer resistance.
  • Categorization of natural compounds into distinct chemical families.
  • Analysis of their impact on cancer cell signaling, drug metabolism, and tumor microenvironment modulation.
  • Exploration of combination therapies and novel drug delivery systems.

Main Results:

  • Natural compounds modulate key cellular processes implicated in therapeutic resistance.
  • Evidence suggests potential for enhancing standard chemotherapy efficacy and overcoming resistance mechanisms.
  • Specific chemical families show promise in targeting cancer cell behavior and tumor microenvironment interactions.
  • Combination therapies and advanced delivery systems are emerging strategies for clinical translation.

Conclusions:

  • Natural bioactive compounds are relevant adjuncts for modern cancer therapy, offering multifaceted mechanisms to combat resistance.
  • Translational research is essential to bridge promising preclinical findings with effective clinical implementation.
  • Further investigation into combination strategies and delivery systems will enhance the therapeutic potential of natural compounds in oncology.
Keywords:
bioactive compoundscancerchemoresistancehealthcaretumor microenvironment

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