The Metabolic Edge: How Cancer Cells Adapt, Survive, and Resist Therapy

Dear Colleagues,

Cancer cells possess a remarkable ability to remodel their metabolism to sustain growth, survive under stress, and ultimately evade therapeutic intervention. This metabolic flexibility—often referred to as metabolic rewiring—provides a crucial survival advantage that underlies both tumor evolution and the emergence of drug resistance. By reshaping nutrient uptake, mitochondrial activity, and biosynthetic and redox pathways, malignant cells can withstand metabolic bottlenecks imposed by targeted therapies and chemotherapy alike.

Recent studies have revealed that therapeutic pressure itself can induce metabolic adaptation, driving the selection of resistant subclones that exploit alternative energy sources or reprogrammed metabolic routes. Such adaptations can reactivate survival signaling, modulate epigenetic states, and alter immune interactions within the tumor microenvironment. These findings highlight metabolism not only as a hallmark of cancer progression but also as a dynamic and targetable contributor to therapy resistance.

The rapid development of genome-scale and precision-editing technologies—including CRISPR/Cas-based functional screens, base editing, and advanced metabolomic approaches—now allows systematic dissection of these adaptive networks across diverse cancer entities. Integrating these techniques with translational and clinical studies is key to identifying metabolic vulnerabilities that can be therapeutically exploited.

This Special Issue invites original research and reviews that explore the role of metabolism in cancer adaptation and therapeutic escape. Areas of interest include nutrient utilization, metabolic signaling, mitochondrial remodeling, redox homeostasis, and therapy-induced metabolic rewiring. Contributions revealing how metabolic pathways enable resistance—and how these dependencies may be overcome—are particularly encouraged.

By illuminating the metabolic strategies that give cancer its edge, this collection aims to foster a deeper understanding of resistance formation and guide the development of novel therapeutic interventions.

Dr. Frank Schnütgen
Guest Editor

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