Fig. 5: Pre-clinical efficacy study in ODInCas9 mouse non-small cell lung cancer model.
From: Development of an ObLiGaRe Doxycycline Inducible Cas9 system for pre-clinical cancer drug discovery
a Timelines for treatment studies. ODInCas9 mice were induced with dox, dosed with AAV, and allocated to treatment arm at 4 weeks KrasG12D;Trp53−/− and 12 weeks KrasG12C;Trp53−/−, when significant tumor burden is observed. KrasG12D;Trp53−/− mice were either killed at 4 weeks for baseline tumor burden or treated for 4 weeks with either vehicle or Docetaxel + Selumetinib combination treatment. Evaluation at baseline and treatment end (T.E) by b lung tissue histology (HE), c MRI, d pERK1/2 immunohistochemical staining. Quantification of tumor burden at baseline, vehicle, and combinatory treatment using e HE histology (one-way ANOVA, F (2, 14) = 5.449, p = 0.0178) and f MRI (two-way ANOVA, F (1, 19) = 5.475, p = 0.0304). Experimental set-up included n = 6 animals per group except HE baseline tumor burden n = 5. MRI vehicle post-treatment had n = 5 as mouse was euthanased due to ethical guidelines. Data are presented as mean values ± SEM.
