Fig. 5: Targeting LOX overcomes chemoresistance in highly aggressive TNBC PDXs.

a Correlation analysis of LOX mRNA expression with hypoxia and focal adhesion scores in 15 different TNBC PDX models. Red dot shows the position of TM01278 PDX model selected. b Representative images of TM01278 PDX organoids at day 0 and day 9 after treatment with doxorubicin and BAPN treatment, alone or in combination. c Quantification of organoid diameter upon combination therapy for 9 days (n = 12 (vehicle, Doxo, BAPN), n = 11 (Doxo+BAPN)). d, e Tumor growth (d) and tumor weight (e) in TM01278 PDX upon treatment with doxorubicin and BAPN, alone or in combination (n = 5). Inset shows LOX expression in PDX tumors. f Representative images of tumors from d. g Relative LOX activity in tumors from d (n = 8 (vehicle), n = 6 (Doxo, BAPN, Doxo+BAPN)). h, i Representative images of Picrosirius red staining (h) and its quantification (i) in combination- and single agent-treated PDX tumors from d (n = 4). j, k Representative images of doxorubicin fluorescence in tumors from d (j), and its quantification (k) (n = 6). l Western blot analysis of FAK/Src signaling in PDXs treated with doxorubicin and BAPN, alone or in combination. Data represents mean ± SD. Two-sided Student’s t-test was used to calculate statistical difference between two groups. One-way ANOVA with Dunnett’s test was performed to compare mean of combination-treated group with single agent treatments in e. Two-way ANOVA test was performed for comparing tumor growth over time among different treatment groups in d. Scale bar = 100 µm for b, 1 cm for f, and 400 µm for h and 200 µm for j. n.s. not significant. Source data are provided as a Source data file.