Fig. 2: RASAL2 promotes pan-resistance to cytotoxic agents beyond platinum.

A Correlation between RASAL2 expression and sensitivity to indicated chemotherapy. The area under percent-viability curves (AUC) was computed as a metric of drug sensitivity, as derived from the Cancer Therapeutics Response Portal. Pearson r and P value are reported. B Cell viability assay. Vector control and RASAL2-overexpressing MDA-MB-468 cells were treated as indicated. Data are represented as mean ± SEM, n = 3 biological replicates. P value by paired T-test. C Spheroid assay. Viability of vector control and RASAL2-overexpressing TNBC spheroids was measured following treatment with vehicle DMSO, doxorubicin (DOXO) or gemcitabine (GEM). Representative images of HCC1806 spheroids are shown. Data are represented as mean ± SEM, n = 3 biological replicates. P value by paired T-test. Scale bar, 250 µm. Cell viability assay. Vector control and RASAL2-overexpressing (D) or -knockdown (E) HCC1937 cells were treated as indicated. Data are represented as mean ± SEM, n = 3 biological replicates. P value by paired T-test. F Correlation between RASAL2 expression and in vivo tumour response to doxorubicin. Mice were treated with vehicle control or 2 mg/kg doxorubicin [22]. Each dot represents an independent TNBC PDX model. Tumour growth inhibition was defined as [1 − (mean volume of treated tumours)/(mean volume of control tumours)] × 100%. Pearson r and P value are reported. G Change in tumour volume following doxorubicin in two TNBC PDX models. Mice were treated as described in (F), n = 8–9 per group. TM00099 tumours had the lowest RASAL2 expression, whereas TM01278 had the highest RASAL2 expression. P value by two-way ANOVA test.