Mechanisms that can lead to drug resistance to PI3K inhibitors in cancer treatment are reported in a study published online this week in Nature Chemical Biology. These findings may help scientists develop strategies to counter resistance before it emerges and thereby improve therapy outcomes for patients.
Mutation of the gene encoding PI3 kinase (PI3K) occurs in more than 25% of breast cancers, which contribute to the malignant growth of the tissue. Inhibitors of PI3K are making their way through clinical trials; however, despite the promise of these therapies, resistance to targeted therapies often emerges.
Sebastian Nijman and colleagues used a chemical genetic approach to predict that activation of the NOTCH1 pathway and the c-MYC gene in breast cancer cells can confer resistance to PI3K inhibitors. The NOTCH pathway had not been linked to PI3K in breast cancer before. The authors believe that by understanding the types of changes that can occur in these tumors during treatment, scientists could better develop strategies for countering resistance to PI3K inhibitors before it emerges.