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@article{194232,
        author = {Antara Ghanta and Rutik Khedekar and Jibin Mathew and Chitra Hemant Kulkarni and Ruchika Kumari and Akshaya Deekonda and Mohammad Shakeeb Khan},
        title = {A Review on Evolutionary Mechanisms of Drug Resistance in Cancer and Therapeutic Approaches},
        journal = {International Journal of Innovative Research in Technology},
        year = {2026},
        volume = {12},
        number = {10},
        pages = {3168-3192},
        issn = {2349-6002},
        url = {https://ijirt.org/article?manuscript=194232},
        abstract = {Cancer drug resistance remains a fundamental challenge in oncology and a primary cause of treatment failure, disease relapse, and cancer-related mortality. Despite substantial progress in chemotherapy, targeted therapy, and immunotherapy, durable clinical responses are often undermined by the emergence of resistant tumor cell populations. Traditional molecular explanations alone fail to fully account for the dynamic and adaptive nature of resistance. Increasing evidence supports the view that cancer progression and therapeutic resistance are governed by evolutionary principles, where genetic diversity, selective pressure imposed by treatment, and tumor microenvironmental factors collectively drive tumor adaptation. Understanding drug resistance through an evolutionary lens has therefore become essential for developing more effective and sustainable therapeutic strategies.
The aim of this review is to comprehensively analyze the evolutionary mechanisms underlying drug resistance in cancer and to critically evaluate current and emerging therapeutic approaches designed to prevent, delay, or overcome resistance. By integrating insights from evolutionary biology, molecular oncology, and clinical therapeutics, this review seeks to provide a unified framework for understanding how resistance arises and how treatment strategies can be optimized to counteract tumor evolution
This review explores both genetic and non-genetic mechanisms that contribute to cancer drug resistance. Genetic mechanisms include point mutations in drug targets, gene amplification, chromosomal instability, and clonal selection of resistant subpopulations. Non-genetic mechanisms such as epigenetic reprogramming, phenotypic plasticity, reversible drug-tolerant states, and the presence of cancer stem cells are also examined in detail. Additionally, the role of tumor heterogeneity both spatial and temporal is highlighted as a critical driver of resistance evolution. The influence of the tumor microenvironment, including hypoxia, immune-mediated selection, stromal interactions, and altered metabolic conditions, is discussed as a key contributor to adaptive resistance. Together, these mechanisms illustrate how cancer behaves as an evolving ecosystem rather than a homogeneous disease entity.
Recognizing drug resistance as an evolutionary process has profound implications for cancer therapy. This review evaluates therapeutic strategies that move beyond conventional maximum tolerated dose approaches, including combination therapy, sequential therapy, adaptive therapy, and evolutionary-informed dosing regimens. The potential of targeting tumor heterogeneity, exploiting fitness trade-offs, and integrating real-time monitoring tools such as liquid biopsies is discussed. Furthermore, the review emphasizes the importance of personalized and evolution-aware treatment strategies to improve long-term disease control. By aligning therapeutic interventions with evolutionary principles, future cancer treatments may achieve greater durability, reduced resistance, and improved patient outcomes.},
        keywords = {Cancer Drug Resistance, Tumor Evolution, Clonal Selection, Genetic Instability, Tumor Heterogeneity, Targeted Therapy, Adaptive Therapy},
        month = {March},
        }