The Genetic Landscape of Cancer Cell Plasticity: Mechanisms, Implications for Therapy Resistance and Emerging Interventions
1 Department of Community Medicine and Primary Health Care, Faculty of Medicine, College of Health Sciences, Nnamdi Azikiwe University, Awka, Nigeria.
2 Department of Healthcare Management, University of New Orleans, Louisiana, USA.
3 Department of Pharmacognosy, Faculty of Pharmaceutical Sciences, University of Port-harcourt, Port-harcourt, Nigeria.
4 Department of Basic Science and Research, Intercountry Centre for Oral Health for Africa, Jos, Nigeria.
5 Department of Human Physiology, Federal University, Lokoja, Nigeria.
6 Department of Biochemistry, Faculty of Basic Medical Sciences, Bayero University, Kano, Nigeria.
7 Department of Computer Science, Manchester Metropolitan University, Manchester, UK
Review
International Journal of Biological and Pharmaceutical Sciences Archive, 2025, 10(02), 065-086.
Article DOI: 10.53771/ijbpsa.2025.10.2.0080
Publication history:
Received on 14 September 2025; revised on 22 October 2025; accepted on 25 October 2025
Abstract:
Cancer cell plasticity, the dynamic ability of tumor cells to switch phenotypic states, drives tumor progression, metastasis, and therapy resistance, posing a formidable challenge to effective cancer management. This review comprehensively explores the genetic and epigenetic mechanisms underlying plasticity, highlighting how oncogenic mutations, chromosomal instability, and pathways like PI3K/AKT and RAS/MAPK enable adaptive behaviors such as epithelial-mesenchymal transition and stemness. Epigenetic regulators, including DNA methylation, histone modifications, and non-coding RNAs, amplify this adaptability, allowing rapid responses to therapeutic pressures. We examine the profound clinical implications, with plasticity fueling relapse in breast, lung, and prostate cancers, exacerbated by tumor microenvironment interactions. Challenges in detecting plastic states due to intratumor heterogeneity underscore the need for advanced diagnostics like single-cell genomics. Emerging interventions, from CRISPR-based gene editing and epigenetic therapies to patient-derived organoids and AI-driven combination strategies, offer transformative potential to disrupt plasticity and overcome resistance. This review illuminates the intricate genetic landscape of cancer cell plasticity, advocating for integrated approaches to revolutionize personalized oncology and improve patient outcomes.
Keywords:
Cancer Cell Plasticity; Tumor Heterogeneity; Therapy Resistance; Genetic Mechanisms; Epigenetic Regulation; Single-Cell Genomics; Targeted Therapies; Patient-Derived Organoids
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Copyright © 2025 Author(s) retain the copyright of this article. This article is published under the terms of the Creative Commons Attribution Liscense 4.0