之前在实验室里的实验表明,两个but not one mutantPIK3CAgene can promote a persistent stem cell state -- a quality called "stemness." But until now, there was no evidence from human patients to support this idea. In the new study, researchers investigate the relationship among PI3K mutations, PI3K activity and stemness in breast cancer. They used publicly available data from nearly 3,000 breast cancer tumors and applied computational methods to infer PI3K activity and stemness. They discovered that aggressive tumors had more PI3K activity and a higher degree of stemness. However, they were surprised to find that cancer cells with only one mutant copy ofPIK3CAhad lower levels of stemness and are potentially less aggressive.

The new study supports the idea that overactive PI3K enzymes are linked to more aggressive breast cancers. Additionally, the researchers warn that the number of copies of mutant PIK3CA mutations in a tumor may affect how it responds to cancer therapies. They conclude that this information, along with data on PI3K activity, should be considered when choosing patients to participate in clinical trials of new drugs.

Madsen adds, "Breast cancer stratification byPIK3CAmutant dose reveals a counterintuitive relationship with functional indices of PI3K pathway activity and tumor dedifferentiation."