Year: 2026
Type: article
Abstract: For decades, cancer cell killing and/or elimination has been the ultimate purpose of cancer therapy.Surgery removes malignant tissue, radiation and chemotherapy destroy rapidly dividing cells, targeted therapies suppress oncogenic signaling, and immunotherapy modulates antitumor immunity.Undoubtedly, these interventions have transformed oncology, but their clinical benefit is often constrained by limited durability, intrinsic resistance, or dose-limiting toxicity.Even in profound clinical responses, residual cancer cells may survive and adapt under therapeutic pressure through cellular plasticity.Cancer reversion challenges this killing/elimination-centered paradigm.Rather than focusing on destroying cancer cells, it aims to redirect them toward a stable differentiated, less tumorigenic, normal-like state ( Fig. 1 A). 1 However, these terms require operational separation.Differentiation induction denotes acquisition of lineage markers or morphology; phenotypic normalization denotes a broader shift toward normal-like transcriptional and cellular features; functional loss of malignancy requires demonstrable reductions in clonogenicity, invasion, tumor initiation or sustained growth; and true durable reversion would additionally require that the same lineage-traced malignant cells maintain a non-malignant state after treatment withdrawal, without continued target suppression.Increased differentiation markers and reduced proliferation alone are therefore insufficient evidence of cancer reversion.Accordingly, conventional differentiation therapy is defined by induction of maturation, whereas a reversion claim additionally requires a quantified shift in cell-state stability and durable functional exit of the same malignant lineage from the malignant attractor; simple cytostasis lacks these state identity and durability criteria.Although conceptually related to differentiation therapy, the application of cancer reversion to solid tumors has been hindered by complex genetic and epigenetic networks, oncogenic signaling, and tissue-specific interactions.1 Two recent studies by the research team of Kwang-Hyun Cho now place this concept on a more systematic and experimentally testable foundation ( Fig. 1 B). 2 , 3 Gong et al. developed single-cell Boolean network inference and control (BENEIN), a framework that reconstructs intestinal differentiation
Language: English
Topic: Cancer Cells and Metastasis
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,160
OpenAlex ID: W7204115948