Pharmacologic inhibitors of PI3Kγ suppress PDAC growth and metastasis.

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Presentation transcript:

Pharmacologic inhibitors of PI3Kγ suppress PDAC growth and metastasis. Pharmacologic inhibitors of PI3Kγ suppress PDAC growth and metastasis. A, merged brightfield and red fluorescent images of mCherry-labeled LMP orthotopic pancreatic tumors from mice that were treated with PI3Kγ inhibitor TG100-115 or chemically similar control according to the schema depicted. B, mean area of fluorescence from A. C, mean weight of pancreata from A. D, incidence of metastases in animals from A. E, weight of normal pancreas and TG100-115 and control-treated p53 2.1.1 orthotopic tumors. F, images of tumors from TG100-115 and control-treated animals from E. Arrows indicate necrotic tissue. G, weight of PDAC tumors from animals treated with saline, TG100-115, gemcitabine (Gem), and gemcitabine + TG100-115 according to the depicted schema. Significance testing was performed by one-sided Anova with Tukey’s post-hoc multiple pairwise testing. H, incidence of metastases in animals from G. Significance testing was performed by the Fisher exact test. I, effect of TG100-115 (n = 9; median survival = 33 days), gemcitabine (n = 9; median survival = 32 days), and combination gemcitabine + TG100-115 treatment (n = 9; median survival = 38 days) on survival of implanted PDAC tumors compared with control-treated animals (n = 9; median survival = 28 days). J, Kaplan–Meier survival plot of KPC animals that were treated from week 10 to week 25 with TG100-115 (n = 5; median survival = 28.5 weeks) compared with control-treated KPC (n = 5; median survival = 21 weeks) and untreated KPC mice (n = 11; median survival = 24.3 weeks). K, incidence of metastasis in TG100-115–treated (n = 15) and control-treated (n = 14) KPC animals. Significance testing was performed by the Fisher exact test. L, images of metastases (arrowheads) in liver cross-sections from control- and TG100-115–treated tumors from K. Megan M. Kaneda et al. Cancer Discov 2016;6:870-885 ©2016 by American Association for Cancer Research