Figure 2.

Efficacy of cisplatin and olaparib in preclinical models and correlation to clinical response. A,In vivo antitumor activity of PARPi (olaparib) and cisplatin in glBRCA PDAC PDXs. Tumor growth (y-axis) for each PDX model after 28 to 52 days (x-axis) of cisplatin (2 mg/kg; i.p.; once weekly) or olaparib (50 mg/kg; i.p.; 5 days on/2 days off) treatment. The dashed line represented a 70% threshold for sensitivity. Columns color code models by the clinical subgroup of response to platinum/PARPi at the time of tissue acquisition (green, sensitive; yellow, refractory; red, acquired resistance; and gray, unknown). B, Tumor growth curves of sensitive (SPC_467; top) and acquired resistance (SPC_187) models. Average relative tumor volume (y-axis) of control, cisplatin-treated (2 mg/kg; i.p; once weekly), and olaparib-treated (50 mg/kg; i.p.; 5 days on/2 days off) mice (n = 6–8 mice/group). C, EVOC H&E representative images of sensitive (SPC_467) and resistant (SPC_187) PDX models. Scale bar indicated in the figure. Insert, magnification ×2.5. D, A 2 × 2 table showing the distribution of responders and nonresponders based on EVOC prediction and clinical actual response to PARPi and platinum agents. E, Correlation between the in vivo and EVOC efficacy for each model and treatment; y-axis, in vivo tumor growth (%); x-axis, EVOC score (0–60 resistant; 61–100 sensitive); black circles [cisplatin (Cis)]; and gray circles [olaparib (Olap)]. r² = 0.59; P < 0.001.