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<p>Glucose-6-phosphate dehydrogenase (G6PD) is the rate-limiting enzyme of pentose phosphate pathway (PPP). It provides essential NADPH for redox balance and ribose-5-phosphate for nucleotide synthesis. Cancer and metastasis are linked to G6PD dysregulation, which allows tumors to progress and tolerate chemotherapy. The molecular mechanisms that hyperactivate G6PD to encourage proliferation, epithelial–mesenchymal transition (EMT), and metastatic niche adaptation are described in this work. Additionally, this review details new post-translational, protein-interaction, and epitranscriptomic control of G6PD and highlights its developing role in cancer. The function of G6PD in nucleotide synthesis and antioxidant defense is being investigated to see if it can lead to resistance to conventional and customized treatments. Lastly, we look at the predictive and therapeutic potential of G6PD. We also discuss new inhibitors and sensible combination strategies that have the potential to transform cancer therapy.</p>

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G6PD: An Old Player with Multiple Emerging Roles from Cancer Progression to Metastasis and Chemoresistance

  • 期刊论文

  • 发表日期：

    2026年7月9日

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  • Lubna Kanwal,
  • Vishal Haer,
  • Habiba Anum,
  • Shaukat Ali

摘要

Glucose-6-phosphate dehydrogenase (G6PD) is the rate-limiting enzyme of pentose phosphate pathway (PPP). It provides essential NADPH for redox balance and ribose-5-phosphate for nucleotide synthesis. Cancer and metastasis are linked to G6PD dysregulation, which allows tumors to progress and tolerate chemotherapy. The molecular mechanisms that hyperactivate G6PD to encourage proliferation, epithelial–mesenchymal transition (EMT), and metastatic niche adaptation are described in this work. Additionally, this review details new post-translational, protein-interaction, and epitranscriptomic control of G6PD and highlights its developing role in cancer. The function of G6PD in nucleotide synthesis and antioxidant defense is being investigated to see if it can lead to resistance to conventional and customized treatments. Lastly, we look at the predictive and therapeutic potential of G6PD. We also discuss new inhibitors and sensible combination strategies that have the potential to transform cancer therapy.