Hsp90α promotes chemoresistance in pancreatic cancer by regulating Keap1-Nrf2 axis and inhibiting ferroptosis

• Hsp90α is significantly upregulated in chemoresistant pancreatic cancer patients and cell lines, correlating with poor prognosis. • Hsp90α promotes chemoresistance by competitively binding to Keap1, leading to Nrf2 nuclear translocation and activation of the GPX4 pathway, which suppresses ferroptosis. • Targeting the Hsp90α-Keap1-Nrf2-GPX4 axis may overcome chemoresistance in pancreatic cancer by restoring ferroptosis sensitivity. • This study provides a theoretical foundation for developing novel therapeutic strategies to improve pancreatic cancer treatment outcomes.