Fig. 7: Synthetic lethality of olaparib plus cisplatin in HRD-positive OS in vitro and in vivo. | Nature Communications

Fig. 7: Synthetic lethality of olaparib plus cisplatin in HRD-positive OS in vitro and in vivo.

From: Multi-omics analysis identifies osteosarcoma subtypes with distinct prognosis indicating stratified treatment

Fig. 7

A Distribution of HRD scores within and across 34 cancer types. The SGH-OS cohort is labeled (orange, n = 107). B Schematic model of the HR and the genomic alterations in the key elements. C Dose response curves and IC50 values of HRD-positive (SA4103), HRD-negative (SA4061) and conventional OS cell lines after 48 h of exposure to the cisplatin and PARP inhibitor olaparib. ****p < 0.0001. Data are shown as mean ± SD. n = 3 independent experiments. P values are derived from two-sided t test. D Synthetic lethality of olaparib plus cisplatin in the SA4103 cell line. Data are shown as mean ± SD. n = 3 independent experiments. The statistical analysis was made by ANOVA with Tukey’s multiple comparisons test. Tumor gross specimen (E) and tumor growth curves (F) in a patient-graft xenograft model treated with olaparib and cisplatin individually or in combination. (n = 5 mice per group). Data are represented as the mean ± SD, P values are derived from two-way ANOVA. *p < 0.05; **p < 0.01; ***p < 0.001. G H&E and immunohistochemical analysis of proliferation (PCNA) and DNA damage (γH2AX) in xenografts. The scale bar represents 50 μM. n = 5 independent experiments. H Body weight changes of xenografts treated with olaparib and cisplatin individually or in combination. Data are shown as the mean ± SD. P values are derived from two-way ANOVA.

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