Tumor hypoxia is main determinant for TH-302 Therapy.
(a-c) Monotherapy TH-302 efficacy in Hs766t (a), MiaPaCa-2 (b) and SU.86.86 (c) tumors (50 mg/kg x 3 days/week x 2 weeks). Black bar represents administration of treatment. N=10 animals per treatment group. (d) Pimonidazole staining as biomarker of physical tumor hypoxia. Pimonidazole Hydrochloride was injected 2hr prior to tumor removal. Scale Bar = 300 μM (e) Carbonic Anhydrase IX (CAIX) staining as biomarker for tumor biological hypoxia. PPC analysis identified Hs766t and MiaPaCa-2 tumors as expressing significantly more CAIX than SU.86.86 tumors. (f) Histological staining of g-H2AX in PDAC tumors pre- and 48hr post-TH-302 treatment (50 mg/kg). (g) Nuclear stain intensity analysis of g-H2AX staining. g-H2AX significantly increased in Hs766t and MiaPaCa-2 Th-302 treated tumors. Data are presented as mean ± S.D of three tumor samples. A two-tailed Student’s t-test was used to determine significance. # p=0.06, ** p<0.01, ***, p<0.001. Scale Bar = 100 μM. See also Additional file 1: Figure S2.