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All cancers fall into just two categories, according to new research from scientists at Sinai Health, with findings that could provide a new strategy for treating the more aggressive and incurable forms of the disease.
In new research published this month in Cancer cell, scientists at the Lunenfeld-Tanenbaum Research Institute (LTRI), part of Sinai Health, divide all cancers into two groups, based on the presence or absence of a protein called Yes-associated protein, or YAP .
Rod Bremner, senior scientist at LTRI, said he has determined that all cancers are present with YAP on or off, and each classification has 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 turned on or off, but it has opposite pro- or anti-cancer effects in both settings,” Bremner said. “So YAPon cancers need YAP to grow and survive. In contrast, YAPoff cancers stop growing when we activate YAP.
Many YAPoff cancers are highly fatal. In their new research, Bremner and his fellow researchers at the Roswell Park Comprehensive Cancer Center in Buffalo, NY, show that certain cancers like prostate and lung can change from a YAPon state to a YAPoff state to resist treatment.
When cancer cells are grown in a dish in the lab, they float or stick. The team of researchers found that YAP is the primary regulator of a cell’s buoyancy, where all floating cells are YAPoff and all sticky cells are YAPon. Changes in adhesive behavior are well known to be associated with drug resistance, so their findings put YAP at the center of that switch, Bremner explained.
Joel Pearson, co-lead author and postdoctoral researcher at LTRI’s Bremner Lab, said therapies that tackle these cancers could have a profound effect on patient survival.
“The simple binary rule that we discovered can outline strategies for treating many types of cancer that fall into the YAPoff or YAPON superclasses,” said Pearson. “Additionally, as cancers jump-stage to escape therapy, having ways to treat the YAPoff and YApon condition could become a general approach to prevent this cancer from changing types to resist drug treatments.”
The researchers hope that by inferring the common vulnerabilities of these types of cancer, it will be possible to develop new therapeutic approaches and improve patient outcomes.
The work was funded primarily by the Canadian Institutes of Health Research (CIHR), the Cancer Research Society and the Krembil Foundation.
Reference: Pearson JD, Huang K, Pacal M et al. Binary pan-cancer classes with distinct vulnerabilities defined by pro- or anti-cancer YAP / TEAD activity. Cancer cell. 2021. doi: 10.1016 / j.ccell.2021.06.016
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