Targeting Cancer Stemness and the Tumor Microenvironment with Functional Biomaterials: The Emerging Role of Plant-Derived Approaches

About this Research Topic

Background

Cancer stem cells (CSCs) and the intricate tumor microenvironment (TME) are central to the persistent challenges of tumor recurrence, metastasis and resistance to therapy. Due to their remarkable adaptability and capacity for self-renewal, CSCs can survive conventional therapies and contribute to tumor regrowth and dissemination. The behavior of the CSC is profoundly influenced by various components of the TME, including immune cells, stromal cells, the extra cellular matrix (ECM), and biochemical gradients such as hypoxia and acidity. These factors not only sustain CSC stemness and tumorigenicity, but also facilitate immune evasion and treatment failure. CSCs possess unique characteristics such as self-renewal, differentiation, and survival under hostile conditions, that are tightly regulated by their niche. Together, these elements orchestrate signaling pathways that drive angiogenesis, tumor progression, and resistance to chemotherapeutic and immunotherapeutic agents.

Recent advances in biomaterials science have enabled the design of functional platforms that replicate key biochemical and biophysical aspects of the TME. These innovative systems serve as powerful tools for investigating CSC behavior, screening potential drugs, and delivering targeted therapies. Notably, plant derived bioactive substances and biomaterials have emerged as promising candidates in this field. These natural substances can modulate the metabolic and epigenetic landscape of CSCs, disrupt critical stemness maintaining pathways (e.g., Hedgehog, Wnt/β-catenin, Notch), and reprogram the TME by reducing inflammation, hypoxia, and acidosis. Such interventions may enhance the efficacy of existing treatments while minimizing toxicity to healthy tissues.

The Research Topic aims to present original and review papers that explore the synergistic interplay between CSC biology, TME modulation, and functional biomaterials with a particular focus on plant-based compounds. We seek to highlight translational strategies, mechanistic insights, and the development of novel biomaterial-based platforms that harness phytochemicals for cancer therapy. By fostering inter-disciplinary collaboration, this collection aspires to advance our understanding of  integrative, nature-based treatments that may overcome the limitations of current cancer therapies and pave the way for more-effective, personalized approaches.

Background (100–150 words)

CSC are in dedicated niches of the tumor microenvironment, where they interact with ECM constituents and stromal cells and receive inputs from soluble factors to promote their stemness and malignancy. The TME is characterized by hypoxia, acidic pH, and chronic inflammation, all of which contribute to CSC survival, immune evasion, and therapeutic resistance. Plant-derived bioactive compounds have shown remarkable potential in modulating both CSCs and the TME, reversing epigenetic dysfunctions, altering cancer metabolism, and sensitizing tumors to treatment. Functional biomaterials synthesized from natural products can be used in vitro to recreate the complex tumor microenvironment and in vivo to deliver targeted cancer therapies. Integrating these strategies is a promising horizon in cancer research.

Goal (100–200 words)

This Research Topic will respond to the critical need for novel therapeutic approaches that modulate both the cancer cell-stemness a well as the tumor microenvironment, which are crucial for tumor progression, metastasis and resistance to therapy. By highlighting the emerging area of plant-derived functional biomaterials, we hope to inspire research at the interface of natural product chemistry, biomaterials engineering, and cancer biology. Our aim is to elucidate mechanisms by which plant-derived molecules and scaffolds can interfere with major stemness pathways, reprogram the TME, and synergize with current treatments to prevent relapse and enhance patient outcome. We aim to offer a forum for innovative research and thought-provoking reviews that will stimulate new translational strategies and assist in building international collaboration in this continually evolving field.

Scope and Information for Authors (100–150 words)

We welcome Original Research, Reviews and Perspectives covering:

• Mechanistic studies on plant-derived compounds that target cancer stem cell pathways.

• Explore biomaterials for enriching or targeting cancer stem cells.

• Modulation of TME components using phytochemical agents.

• Translational and preclinical studies on plant-based therapeutics in combination with conventional treatments.

• Innovative biomaterial platforms for drug delivery or TME modelling.

Submissions should present rigorous, hypothesis-driven work with clear mechanistic or translational relevance. Interdisciplinary collaborations and studies that bridge multiple fields are highly encouraged.

Article types and fees

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Data Report
• Editorial
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• Original Research
• ... View all formats

Articles that are accepted for publication by our external editors following rigorous peer review incur a publishing fee charged to Authors, institutions, or funders.

Article types

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Data Report
• Editorial
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• Original Research
• Perspective
• Review
• Technology and Code

Keywords: Cancer stem cells; Tumor microenvironment; Extracellular matrix; Plant-derived compounds; Biomaterials

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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