Stemness and Cell Plasticity : Non-genetic Drivers of Therapy Resistance in Hematologic and Solid Malignancies

Cancer progression and relapse arise not only from genetic evolution but also from dynamic, reversible cell-state transitions that enable malignant cells to adapt under therapeutic pressure. Across solid tumors and hematologic malignancies, malignant cells can acquire stem-cell-like properties, including self-renewal, differentiation blockade, quiescence/dormancy, and enhanced stress tolerance, and undergo lineage plasticity or therapy-induced fate changes. These processes can enable escape from targeted therapies, chemotherapy, and immunotherapies, contribute to minimal residual disease, and ultimately promote treatment-refractory relapse.This Collection will focus on the mechanistic basis of stemness and cell plasticity as drivers of therapy resistance, with an emphasis on studies that resolve tumor heterogeneity and resistant cell states using advanced experimental model systems and state-resolved approaches. We particularly welcome submissions that connect phenotype transitions to defined, testable molecular regulators, spanning transcriptional and epigenetic control, developmental signaling pathways, metabolic rewiring, stress-response programs, and microenvironmental cues, and that provide experimentally validated evidence for how these mechanisms can be therapeutically targeted to improve treatment outcomes. We welcome studies dissecting non-genetic mechanisms of therapy resistance, including epigenetic memory, chromatin remodeling, transcriptional reprogramming, and adaptive stress-response networks.We invite contributions spanning hematologic malignancies (including but not limited to AML, ALL, MDS/MPN, lymphoma, and myeloma) and relevant solid-tumor contexts, with priority given to mechanistic insights that generalize across disease types. We especially encourage studies that compare, translate, or generalize resistance-associated cell states and regulatory circuits across hematologic and solid malignancies (e.g., persister programs, cell-fate control networks, and non-genetic adaptation under therapy). Submissions that explicitly relate malignant stem-like programs to normal stem cell biology (e.g., hijacking of developmental pathways, altered differentiation trajectories, or niche mimicry) are particularly encouraged. Topic editors: Naisana Seyedasli, MARIANGELA PALLADINO Source: https://www.frontiersin.org/research-topics/78549/stemness-and-cell-plasticity-non-genetic-drivers-of-therapy-resistance-in-hematologic-and-solid-malignancies