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PI3K/AKT pathway and hormone therapy resistance. The interaction between ER signaling and the RTK pathway is considered a major mechanism of resistance to hormone therapy. Upregulation of both the PI3K/AKT/mTOR and RAS/RAF/MAPK pathways activates the ERα-independent pathway in the absence of estrogen though extranuclear ER signaling, thus causing estrogen-regulated gene activation that ultimately promotes cancer cell survival and leads to hormone therapy resistance.
