THRB and cancer: Moreover, THRB-PV, a THRB mutant that shows loss of T3 binding ability but interacts more significantly with the PI3K regulatory subunit, p85, triggers a greater increase in PI3K kinase activity and activation of the PI3K-AKT- mTOR-p70S6K pathway in cytoplasmic and nuclear compartments, with predisposition to tumor development in several cancer types, including thyroid and mammary tumors [75, 76].