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

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.