Fig. 8: PDxO screening can be performed in real time with clinical care.
a, Timeline of the individual HCI-043, including clinical history, patient-derived model establishment (PDX and PDxO est.), PDxO drug screens and in vivo validation of responses in PDX. Model development and drug screening/testing were done with both the pretreatment biopsy sample (HCI-043) and the metastatic ascites sample (HCI-051), with similar results. ddAC, dose-dense doxorubicin and cyclophosphamide. b, Treatment of the HCI-043 PDX with human-matched neoadjuvant therapy (doxorubicin + cyclophosphamide followed by paclitaxel (AC-T); left) or with drugs selected from the PDxO screen (right). Arrows indicate the sequencing of AC-T drug treatment. Data are shown as mean ± s.e.m.; left: AC-T treatment group, n = 5 mice; vehicle group, n = 4 mice; right: cabozantinib, n = 4 mice; talazoparib, n =4 mice; enzalutamide, n = 4 mice; eribulin, n = 5 mice; vehicle group, n = 8 mice. c, Follow-up of HCI-043 PDX mice after stopping treatment with eribulin following three doses. Two different mice (ms) exhibited recurrence off-treatment, but the tumors regressed after treatment was restarted. No resistant tumors were detected over the lifespan of the mice (293 d after initial treatment began). d, Treatment of HCI-051 PDX with AC-T, as in b. Data are shown as mean ± s.e.m.; treatment and vehicle groups, n = 5 mice for all PDX lines.
