Science: new drug combinations can overcome drug-resistant cancer cells

August 28, 2019 / bioin / - cancer cells can adapt to and develop resistance to chemotherapy drugs, which makes it difficult to eradicate tumors A new study led by researchers at Brigham women's hospital shows that a combination of three drugs, including a new glucose-6-phosphate dehydrogenase inhibitor, can overcome cross treatment resistance The results of the study were recently published in the journal Science signaling "We have only recently begun to unravel the full complexity of chemotherapy failure," said Dr Aaron Goldman, a medical lecturer in the bioengineering Department of Brigham and women's hospital "As far as the source of resistance is concerned, the drug itself is part of the problem Drug resistance is not just inherent in cells "Researchers used computational models, in vitro experiments, in vivo animal models, clinical explants, and in vitro models of human tumors to explore the metabolic process of chemotherapy drug tolerance Based on Warburg effect, a widely accepted example of drug resistance, the researchers observed that cancer cells absorbed extra glucose, leading to overload of glycolysis pathway But contrary to Warburg's effect, the researchers found increased mitochondrial activity, indicating a high oxygen consumption of cells Using mathematical models, Goldman and his team found that in a time sensitive process, a combination of three drugs sensitized cancer cells In addition to these new drugs, a combination of clinically available drugs can also be used to fight resistance, Goldman said The researchers acknowledge that they have not yet had a clear understanding of the plasticity of cancer cells, which allows them to acquire new metabolic phenotypes and develop resistance In the future, researchers hope to use mathematical models and machine learning to develop more and more accurate drug solutions to provide information for new cancer treatment "We are modeling the biological framework mathematically, which will allow us to predict the drug sequence," Goldman said "We're not just putting drugs together - we're developing a combination of rational responses to resistance "Reference: Aaron Goldman et al Targeting tumor phenotypic city and metallic remodelling in adaptive cross drug tolerance," Science Signaling 20 Aug 2019: Vol 12, issue 595, eaas8779 doi: 10.1126/scientific.aas8779