The pentose phosphate pathway (PPP) is a critical metabolic pathway in cancer cells, providing NADPH for fatty acid synthesis and antioxidant defense. It also generates ribonucleotides essential for DNA and RNA synthesis. The PPP has two branches: the oxidative branch, which produces NADPH and ribonucleotides, and the nonoxidative branch, which facilitates the conversion of sugars into pentose phosphates. The PPP is regulated by various enzymes, including glucose-6-phosphate dehydrogenase (G6PDH), 6-phosphogluconate dehydrogenase (6PGDH), transketolase (TKT), and transaldolase (TALDO). These enzymes are regulated by multiple mechanisms, including posttranslational modifications and signaling pathways. Cancer cells often upregulate the PPP to meet their high anabolic demands and combat oxidative stress. Tumor suppressors like p53 and oncogenes such as Ras regulate the PPP to support cancer cell survival and proliferation. p53 can inhibit the PPP to reduce ROS and promote cell survival, while Ras activates the PPP to enhance NADPH production. The PPP is also regulated by the mTORC1 pathway and the Nrf2 transcription factor, which are involved in metabolic reprogramming in cancer cells. The PPP is essential for cancer cell survival and metastasis, as it provides NADPH for antioxidant defense and nucleotide synthesis. However, targeting the PPP for cancer therapy is challenging due to its critical role in cancer cell metabolism. Despite this, some studies suggest that modulating the PPP could be a potential therapeutic strategy. The PPP's role in cancer is complex, with different enzymes and pathways involved in its regulation. Understanding the PPP's functions and regulation in cancer cells is crucial for developing effective therapeutic strategies.The pentose phosphate pathway (PPP) is a critical metabolic pathway in cancer cells, providing NADPH for fatty acid synthesis and antioxidant defense. It also generates ribonucleotides essential for DNA and RNA synthesis. The PPP has two branches: the oxidative branch, which produces NADPH and ribonucleotides, and the nonoxidative branch, which facilitates the conversion of sugars into pentose phosphates. The PPP is regulated by various enzymes, including glucose-6-phosphate dehydrogenase (G6PDH), 6-phosphogluconate dehydrogenase (6PGDH), transketolase (TKT), and transaldolase (TALDO). These enzymes are regulated by multiple mechanisms, including posttranslational modifications and signaling pathways. Cancer cells often upregulate the PPP to meet their high anabolic demands and combat oxidative stress. Tumor suppressors like p53 and oncogenes such as Ras regulate the PPP to support cancer cell survival and proliferation. p53 can inhibit the PPP to reduce ROS and promote cell survival, while Ras activates the PPP to enhance NADPH production. The PPP is also regulated by the mTORC1 pathway and the Nrf2 transcription factor, which are involved in metabolic reprogramming in cancer cells. The PPP is essential for cancer cell survival and metastasis, as it provides NADPH for antioxidant defense and nucleotide synthesis. However, targeting the PPP for cancer therapy is challenging due to its critical role in cancer cell metabolism. Despite this, some studies suggest that modulating the PPP could be a potential therapeutic strategy. The PPP's role in cancer is complex, with different enzymes and pathways involved in its regulation. Understanding the PPP's functions and regulation in cancer cells is crucial for developing effective therapeutic strategies.