All cancers fall into just two categories. It is the incredible result of new research by scientists at Sinai Health, and it could provide a new strategy for treating the most aggressive and untreatable forms of the disease.
In new research published this month on Cancer Cell, scientists of the Lunenfeld-Tanenbaum Research Institute (LTRI), part of Sinai Health, divide all tumors into two groups, based on the presence or absence of a protein called YAP.
The study follows the results on the interaction between YAP and tumors obtained in recent years. In this case, by 3 very talented Italian researchers from the University of Padua: Francesca Zanconato, Michelangelo Cordenonsi e Stefano Piccolo, in this study.
Does a single protein determine, with its presence or absence, all tumors?
Rod Bremner, senior scientist at LTRI, said they have determined that all tumors are present with YAP enabled or disabled. Each of these classifications shows 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 so-calledHippo signaling route”. It is a mechanism that regulates cell proliferation (for better or for worse…)
“Not only is YAP off or on, but it has opposite pro- or anti-cancer effects in both contexts,” Bremner says. “Therefore, tumors with YAP turned on need YAP to grow and survive. In contrast, tumors with YAP quenched they stop growing when we turn on YAP.
Tumors "turn off" the protein to resist treatment – The news is potentially excellent, because many of the tumors with YAP off are highly lethal. In their new research, Bremner and the other researchers show that some cancers, such as prostate and lung cancer, can switch from a “YAP on” state to a “YAP off” state to resist treatment.
Studies in the laboratory
When cancer cells are grown in a Petri dish in the laboratory, they float or stick together. The research team found that YAP is the master regulator of a cell's buoyancy. All “floating” cells have YAP off and all “sticky” cells have YAP on. As changes in cell adherence are known to be associated with drug resistance, the finding implies that YAP is at the heart of this switch.
Joel Pearson, co-lead author of the study, says therapies for these cancers could have a profound effect on patient survival.
The simple binary rule we discovered can give rise to many strategies for treating cancer types that fall into the “YAP on” or “YAP off” superclasses. Furthermore, as tumors change states to evade therapy, having ways to treat both states could become a general approach to preventing this cancer from resisting treatments.
Joel Pearson