First described by Otto Warburg a century ago, the Warburg Effect refers to cancer cells' preference for aerobic glycolysis over oxidative phosphorylation, even when oxygen is available. This metabolic reprogramming allows for rapid energy production and biomass synthesis, supporting uncontrolled growth and survival in challenging microenvironments. Modern research has shown that oncogenes and tumor suppressors closely regulate these metabolic changes. Besides fueling growth, altered metabolism also plays a role in therapy resistance, immune evasion, and tumor progression. As understanding advances, targeting cancer metabolism has become a promising approach for prevention and treatment, making the Warburg Effect a key concept in exploring new directions in cancer biology and therapy.

Although the Warburg Effect has been recognized for a century, transforming this metabolic hallmark into effective clinical treatments remains challenging. Cancer metabolism is highly adaptable and varies across tumor types and microenvironments, leading to therapeutic resistance and limited success of current metabolic inhibitors. Furthermore, the interactions among tumor metabolism, the immune system, and stromal cells remain poorly understood. This research field aims to address these gaps by encouraging studies that combine multi-omics, metabolomics, and advanced imaging to map metabolic diversity and identify targets. Recent advances, including single-cell and spatial metabolomics, hyperpolarized C imaging, and clinical trials targeting enzymes like IDH, LDH, and glutaminase, offer promising new directions. By integrating mechanistic, translational, and clinical perspectives, this issue seeks to accelerate the development of metabolism-based biomarkers, combination therapies, and personalized approaches to overcome resistance and enhance cancer prevention and treatment outcomes.

This special issue invites contributions that enhance our understanding of cancer metabolism and its translational applications. We welcome original research articles, reviews, short communications, and perspectives on, but not limited to, the following themes:

• Molecular and genetic regulation of the Warburg Effect and metabolic reprogramming.

• Crosstalk among cancer metabolism, tumor microenvironment, and immune response.

• Novel biomarkers and imaging techniques for metabolic profiling.

• Targeting metabolic enzymes and pathways for cancer prevention and treatment.

• Dietary and pharmacological interventions for metabolism.

• Clinical and translational research on metabolism-driven cancer therapies.

This Special Issue aims to combine fundamental discoveries with therapeutic innovation, encouraging collaboration among researchers in cancer biology, molecular medicine, and clinical oncology.

Please note that manuscripts consisting solely of bioinformatics or computational analysis of public omics databases that are not supplemented by relevant functional validation (clinical cohort or biological validation in vitro or in vivo) are out of scope for this Research Topic.

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Hundred Years of The Warburg Effect, Metabolic Hallmark of Cancer Cells: Progress in the Prevention, Treatment and Targeted Therapy of Cancer