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Review

Beyond eradication: Therapeutic reprogramming strategies for cancer normalization (Review)

  • Authors:
    • Aliasgar Shahiwala
  • View Affiliations / Copyright

    Affiliations: Department of Pharmaceutical Sciences, College of Pharmacy, Dubai Medical University, Dubai, United Arab Emirates
  • Article Number: 29
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    Published online on: December 4, 2025
       https://doi.org/10.3892/or.2025.9034
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Abstract

Cancer is increasingly recognized not as a fixed genetic condition but as a dynamic and plastic disease state driven by reversible epigenetic, transcriptional and microenvironmental cues. This evolving understanding supports a therapeutic paradigm shift: from eradicating malignant cells to reprogramming them toward quiescence, differentiation or functional normalization. This review explores diverse strategies for redirecting cancer cell fate, including differentiation therapy, epigenetic remodeling, lineage reprogramming, senescence induction and tumor microenvironment resetting. These approaches exploit intrinsic cellular plasticity and contextual adaptability, offering novel avenues to contain malignancy and overcome resistance. By reframing cancer as a potentially reversible phenotype, this therapeutic strategy demands redefinition of clinical endpoints, incorporation of dynamic biomarkers, and development of integrative treatment frameworks. Ultimately, reprogramming‑based oncology holds the promise of transforming aggressive malignancies into manageable conditions while minimizing the collateral damage associated with conventional cytotoxic therapies.
View Figures

Figure 1

Life cycle of cancer cells. Normal
cells undergo transformation and clonal evolution, driven by
microenvironmental factors such as inflammation, hypoxia,
epithelial-to-mesenchymal transition and immune evasion, leading to
invasion, metastasis and eventual dormancy.

Figure 2

Reprogramming strategies for cancer
reversal. Therapeutic reprogramming of cancer cells through
differentiation, senescence, lineage conversion, epigenetic
modulation or microenvironmental reset to restore normal or
nonmalignant states.
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Copy and paste a formatted citation
Spandidos Publications style
Shahiwala A: Beyond eradication: Therapeutic reprogramming strategies for cancer normalization (Review). Oncol Rep 55: 29, 2026.
APA
Shahiwala, A. (2026). Beyond eradication: Therapeutic reprogramming strategies for cancer normalization (Review). Oncology Reports, 55, 29. https://doi.org/10.3892/or.2025.9034
MLA
Shahiwala, A."Beyond eradication: Therapeutic reprogramming strategies for cancer normalization (Review)". Oncology Reports 55.2 (2026): 29.
Chicago
Shahiwala, A."Beyond eradication: Therapeutic reprogramming strategies for cancer normalization (Review)". Oncology Reports 55, no. 2 (2026): 29. https://doi.org/10.3892/or.2025.9034
Copy and paste a formatted citation
x
Spandidos Publications style
Shahiwala A: Beyond eradication: Therapeutic reprogramming strategies for cancer normalization (Review). Oncol Rep 55: 29, 2026.
APA
Shahiwala, A. (2026). Beyond eradication: Therapeutic reprogramming strategies for cancer normalization (Review). Oncology Reports, 55, 29. https://doi.org/10.3892/or.2025.9034
MLA
Shahiwala, A."Beyond eradication: Therapeutic reprogramming strategies for cancer normalization (Review)". Oncology Reports 55.2 (2026): 29.
Chicago
Shahiwala, A."Beyond eradication: Therapeutic reprogramming strategies for cancer normalization (Review)". Oncology Reports 55, no. 2 (2026): 29. https://doi.org/10.3892/or.2025.9034
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