YAP Gene Helps Classify Cancers

According to new research from scientists at Sinai Health, all cancers fall into just two categories in findings that could provide a new strategy for treating the most aggressive and untreatable forms of the disease. Their findings were published in Cancer Cell. 

Rod Bremner, the lead researcher, said they have determined that all cancers are present with YAP either on or off, and each classification exhibits different drug sensitivities or resistance. YAP plays an important role in the formation of malignant tumors because it is an important regulator and effector of the Hippo signaling pathway. "Not only is YAP either off or on, but it has opposite pro- or anti-cancer effects in either context," Bremner said. "Thus, YAPon cancers need YAP to grow and survive. In contrast, YAPoff cancers stop growing when we switch on YAP."

In their new research, Bremner and fellow researchers from the Roswell Park Comprehensive Cancer Center in Buffalo, NY, show that some cancers like prostate and lung can jump from a YAPon state to a YAPoff state to resist therapeutics. The team of researchers found that YAP is the master regulator of a cell's buoyancy, where all the floating cells are YAPoff, and all the sticky cells are YAPon. Changes in adhesive behavior are well known to be associated with drug resistance, so their findings implicate YAP at the hub of this switch, explained Bremner.

Co-lead author Joel Pearson added that "The simple binary rule we uncovered may expose strategies to treat many cancer types that fall into either the YAPoff or YAPon superclasses," Pearson said. "Moreover, since cancers jump states to evade therapy, having ways to treat either the YAPoff and YAPon state could become a general approach to stop this cancer from switching types to resist drug treatments," he concluded.