Epithelial–mesenchymal transition and cancer-associated fibroblasts in tumor progression and therapy resistance: mechanistic convergence and therapeutic opportunities

• Dhiraj Kumar Singh ^[2] ; Rashmi Gupta ^[3] ; Umesh Kumar ^[4] ; Saurabh Gupta ^[1]
  1. [1] GLA University

     GLA University

     India

     
  2. [2] Department of NMR, All India Institute of Medical Sciences Delhi, New Delhi, India
  3. [3] Department of Biochemistry, All India Institute of Medical Sciences Delhi, New Delhi, India
  4. [4] Chandigarh University, NH5, Chandigarh–Ludhiana Highway, Gharuan, Mohali, Punjab, India

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• Localización: Clinical & translational oncology, ISSN 1699-048X, Vol. 28, Nº. 8, 2026, págs. 3086-3091
• Idioma: inglés
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• Resumen

  • Cancer progression and treatment failure are driven not only by tumor-intrinsic alterations but also by dynamic interactions within the tumor microenvironment (TME). Epithelial–mesenchymal transition (EMT) and cancer-associated fibroblasts (CAFs) represent two interlinked mechanisms that promote tumor invasion, metastatic dissemination, stemness, immune evasion, and resistance to therapy. EMT is regulated by transcription factors, such as Snail, ZEB, and Twist, and by signaling pathways including TGF-β, Wnt/β-catenin, and Notch, enabling cancer cells to adopt hybrid epithelial–mesenchymal states that confer phenotypic plasticity and drug tolerance. CAFs, derived from multiple cellular sources, further reinforce EMT programs through paracrine signaling, extracellular matrix remodeling, and metabolic reprogramming. This review critically synthesizes current evidence on EMT–CAF crosstalk in oncogenesis and therapeutic resistance, highlighting emerging clinical strategies, translational challenges, and lessons from failed or limited therapeutic approaches. By emphasizing EMT plasticity and CAF heterogeneity as convergent drivers of tumor adaptability, this work provides a refined framework for developing rational combination therapies targeting both cancer cells and their supportive stroma.