The Warburg effect, first observed by Otto Warburg in 1924, refers to the tendency of cancer cells to metabolize glucose through aerobic glycolysis rather than oxidative phosphorylation, even in the presence of oxygen. This phenomenon has been the subject of extensive research, revealing that cancer cells prioritize the uptake and incorporation of nutrients into biomass for cell proliferation rather than maximizing ATP production. This metabolic adaptation is supported by evidence showing that signaling pathways involved in cell proliferation also regulate metabolic pathways that support biomass synthesis. Additionally, certain cancer-associated mutations enable cancer cells to metabolize nutrients in a way that supports proliferation rather than efficient ATP production. In contrast to normal differentiated cells, which rely on mitochondrial oxidative phosphorylation for energy, proliferating cells, including cancer cells, use aerobic glycolysis to generate the necessary building blocks for cell division. This metabolic strategy, while less efficient in ATP production, allows for the rapid synthesis of nucleotides, amino acids, and lipids required for cell growth. The Warburg effect is not solely due to mitochondrial dysfunction but is instead a metabolic adaptation that supports the high demand for biomass synthesis in proliferating cells. The metabolic needs of proliferating cells extend beyond ATP production, requiring significant amounts of NADPH and carbon for macromolecular synthesis. This is achieved through the diversion of glucose into biosynthetic pathways, such as the pentose phosphate shunt and lipid synthesis. The production of lactate and alanine during aerobic glycolysis provides NADPH, which is essential for macromolecular synthesis and redox control. This metabolic strategy is particularly advantageous in environments where nutrients are abundant, as it allows for rapid cell division without the need for optimal ATP yield. The regulation of cellular metabolism is closely linked to cell growth and survival. Signaling pathways such as PI3K/Akt and Myc play critical roles in controlling glucose uptake, metabolism, and the redirection of metabolic intermediates toward biosynthetic pathways. These pathways are essential for the survival and proliferation of cancer cells, which have evolved to bypass normal growth factor dependence through genetic mutations. Understanding the metabolic requirements of proliferating cells may lead to the development of novel cancer therapies targeting metabolic pathways. The metabolic adaptations of cancer cells, including the Warburg effect, have significant implications for cancer treatment. Targeting metabolic pathways such as glycolysis, NADPH production, and glutamine metabolism may provide new therapeutic strategies. Additionally, the role of metabolic diseases such as diabetes in cancer predisposition highlights the importance of understanding the interplay between whole-body metabolism and tumor metabolism. Future research aims to further elucidate the complex relationship between metabolism and cell proliferation, potentially leading to more effective cancer treatments.The Warburg effect, first observed by Otto Warburg in 1924, refers to the tendency of cancer cells to metabolize glucose through aerobic glycolysis rather than oxidative phosphorylation, even in the presence of oxygen. This phenomenon has been the subject of extensive research, revealing that cancer cells prioritize the uptake and incorporation of nutrients into biomass for cell proliferation rather than maximizing ATP production. This metabolic adaptation is supported by evidence showing that signaling pathways involved in cell proliferation also regulate metabolic pathways that support biomass synthesis. Additionally, certain cancer-associated mutations enable cancer cells to metabolize nutrients in a way that supports proliferation rather than efficient ATP production. In contrast to normal differentiated cells, which rely on mitochondrial oxidative phosphorylation for energy, proliferating cells, including cancer cells, use aerobic glycolysis to generate the necessary building blocks for cell division. This metabolic strategy, while less efficient in ATP production, allows for the rapid synthesis of nucleotides, amino acids, and lipids required for cell growth. The Warburg effect is not solely due to mitochondrial dysfunction but is instead a metabolic adaptation that supports the high demand for biomass synthesis in proliferating cells. The metabolic needs of proliferating cells extend beyond ATP production, requiring significant amounts of NADPH and carbon for macromolecular synthesis. This is achieved through the diversion of glucose into biosynthetic pathways, such as the pentose phosphate shunt and lipid synthesis. The production of lactate and alanine during aerobic glycolysis provides NADPH, which is essential for macromolecular synthesis and redox control. This metabolic strategy is particularly advantageous in environments where nutrients are abundant, as it allows for rapid cell division without the need for optimal ATP yield. The regulation of cellular metabolism is closely linked to cell growth and survival. Signaling pathways such as PI3K/Akt and Myc play critical roles in controlling glucose uptake, metabolism, and the redirection of metabolic intermediates toward biosynthetic pathways. These pathways are essential for the survival and proliferation of cancer cells, which have evolved to bypass normal growth factor dependence through genetic mutations. Understanding the metabolic requirements of proliferating cells may lead to the development of novel cancer therapies targeting metabolic pathways. The metabolic adaptations of cancer cells, including the Warburg effect, have significant implications for cancer treatment. Targeting metabolic pathways such as glycolysis, NADPH production, and glutamine metabolism may provide new therapeutic strategies. Additionally, the role of metabolic diseases such as diabetes in cancer predisposition highlights the importance of understanding the interplay between whole-body metabolism and tumor metabolism. Future research aims to further elucidate the complex relationship between metabolism and cell proliferation, potentially leading to more effective cancer treatments.