2019/08/20 by Aaron Goldman, Sachin Khiste, Elizaveta Freinkman +13 · 1 citation
Biochemistry, Genetics and Molecular Biology · #Cancer, Hypoxia, and Metabolism #Metabolism, Diabetes, and Cancer #Epigenetics and DNA Methylation
paper · doi:10.1126/scisignal.aas8779
openalex publication_date 2019/08/20 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/22
phenotype to increased activity of both the glycolytic and oxidative pathways and glucose flux through the pentose phosphate pathway (PPP). When given in a specific order, a combination of taxanes, anthracyclines, and inhibitors of glucose-6-phosphate dehydrogenase (G6PD), an enzyme involved in glucose metabolism, improved survival in mouse models of breast cancer. The same sequence of the three-drug combination reduced the viability of patient breast tumor samples in an explant system. Our findings highlight a convergence between phenotypic and metabolic state transitions that confers a survival advantage to cancer cells against clinically used drug combinations. Pharmacologically targeting this convergence could overcome cross-drug tolerance and could emerge as a new paradigm in the treatment of cancer.