a PCR array for CSC and self-renewal markers in SP/CSC cells (SP-SW1990) after 4 days of treatment with afatinib. b RT-PCR analysis showing downregulation of FOXA2 and SOX9 mRNA (Top 3 images) and immunoblot analysis of FOXA2 and β-actin (loading control) proteins (bottom 2 blots) in PCSC in response to afatinib treatment. c Transient suppression of EGFR in SP-SW1990 cells and its effects on CSC markers (FOXA2, SOX9, DCAMLK1, NANOG, and OCT4) and oncogenic signaling molecules (pERK) along with a reduction of total EGFR protein. d Immunoblot analysis of PCSC cells transiently knockdown for FOXA2 and its impact on SOX9 protein. e Immunoblot analysis showing a reduction in FOXA2 and SOX9 protein expression upon dose-dependent (IC20 and IC50 concentrations) treatments with afatinib alone in SPPC cells. f Immunofluorescence analysis of FOXA2 and SOX9 protein co-expression in afatinib-treated KPC tumoroids and mouse primary xenograft tumors. g Immunoblot analysis of FOXA2 and SOX9 protein expression in PC cells treated with afatinib/gemcitabine alone and combination therapies. h Schematic model of the hypothesized signaling axis by which afatinib inhibits the PCSC, scale bars= 5 μM and 2 μM.