Academic Journal
Developmentally constrained plasticity as a therapeutic vulnerability in cancer.
| Τίτλος: | Developmentally constrained plasticity as a therapeutic vulnerability in cancer. |
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| Συγγραφείς: | Xian JS; The First Clinical School of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, 511436, China., Yang YX; Department of Obstetrics, Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, China., Li WL; Guangzhou Municipal and Guangdong Provincial Key Laboratory of Protein Modification and Degradation, School of Basic Medical Science, Guangzhou Medical University, Guangzhou, 511436, China., Liu M; Guangzhou Municipal and Guangdong Provincial Key Laboratory of Protein Modification and Degradation, School of Basic Medical Science, Guangzhou Medical University, Guangzhou, 511436, China; Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, 510095, China. Electronic address: liuming@gzhmu.edu.cn., Zhang XF; Department of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, China; Guangzhou Municipal and Guangdong Provincial Key Laboratory of Protein Modification and Degradation, School of Basic Medical Science, Guangzhou Medical University, Guangzhou, 511436, China; Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, 510095, China. Electronic address: cheungXF@gzhmu.edu.cn. |
| Πηγή: | Neoplasia (New York, N.Y.) [Neoplasia] 2026 Oct; Vol. 80, pp. 101344. Date of Electronic Publication: 2026 Jul 29. |
| Τύπος έκδοσης: | Journal Article; Review; Research Support, Non-U.S. Gov't |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Elsevier Country of Publication: United States NLM ID: 100886622 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1476-5586 (Electronic) Linking ISSN: 14765586 NLM ISO Abbreviation: Neoplasia Subsets: MEDLINE |
| Imprint Name(s): | Publication: 2014- : [Amsterdam] : Elsevier Original Publication: New York, NY : Stockton Press, c1999- |
| Ιατρικοί όροι (MeSH): | Neoplasms*/pathology , Neoplasms*/etiology , Neoplasms*/therapy , Neoplasms*/drug therapy , Neoplasms*/metabolism , Cell Plasticity*, Drug Resistance, Neoplasm/genetics ; Cell Transformation, Neoplastic/genetics ; Cell Transformation, Neoplastic/metabolism ; Humans ; Animals ; Cell Lineage ; Cellular Reprogramming |
| Περίληψη: | Cancer cells can exploit developmental lineage programs to generate phenotypic heterogeneity under therapeutic pressure. Although a subset of resistant tumors preserves its founding lineage, receptor, or oncogenic dependency, accumulating evidence shows that others enter reversible persister states or stabilize alternative lineage programs. Here we frame malignant plasticity as developmentally constrained, not limitless: cell of origin, lineage history, injury memory, genetic gates, chromatin state, transcription-factor circuits, and tumor-ecosystem feedback help delimit and probabilistically bias which state transitions are accessible under therapy. We distinguish physiological expansion of state space during repair from premalignant permissiveness and malignant fixation, and classify resistance into three modes: lineage-maintained resistance, adaptive reversible plasticity, and fixed reprogramming through lineage switching or histological transformation. These modes should be read as diagnoses rather than rigid therapeutic silos. Prime-then-kill strategies are most defensible when a resistant state is reversible, targetable, and paired with readouts; they may also be considered as biomarker-defined add-on hypotheses in lineage-maintained or lineage-rerouted disease when an evidence-supported state or immune-visibility module is present. Conversely, tumors that retain driver, receptor, or lineage dependency should keep the preserved axis or bypass pathway as the therapeutic backbone, and fixed histological transformation often requires treatment according to the new lineage. We also discuss how single-cell and spatial multi-omics can map state-space breadth and ecosystem context and, when paired with perturbational designs, help test transition capacity and reversibility; static marker expression alone cannot establish plasticity. A resistance-mode-guided approach can sharpen therapeutic hypotheses and limit overgeneralization across tumor types. (Copyright © 2026. Published by Elsevier Inc.) |
| Competing Interests: | Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Xiao-Feng Zhang reports financial support was provided by National Natural Science Foundation of China. Ming Liu reports financial support was provided by National Natural Science Foundation of China. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. |
| Contributed Indexing: | Keywords: Cancer plasticity; Cell of origin; Developmental constraint; Drug-tolerant persisters; Lineage switching; Therapeutic resistance |
| Entry Date(s): | Date Created: 20260729 Date Completed: 20260901 Latest Revision: 20260918 |
| Update Code: | 20260919 |
| PubMed Central ID: | PMC13449346 |
| DOI: | 10.1016/j.neo.2026.101344 |
| PMID: | 42526354 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1476-5586 |
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| DOI: | 10.1016/j.neo.2026.101344 |