220 POSTER Combination of class I PI3K inhibitor, GDC-0941, with standard of care therapeutics results in enhanced anti-tumor responses in human cancer models in vitro and in vivo

Targeting the PI3K/AKT/mTOR Pathway in Cancer Cells

“…In biochemical assays, pictilisib demonstrates selectivity over a large panel of protein kinases and PI3K family kinases, including mTOR and DNA-dependent protein kinase (DNA-PK) [75]. Interestingly, pictilisib induces apoptosis in a subset of human tumor cell lines and potently inhibited tumor growth in xenograft models, including those with mutations in PI3K, PTEN, and K-Ras [76]. Significant in vivo antitumor activity has also been observed when administered orally in combination with other anticancer drugs, for example, docetaxel and MEK inhibitor U0126 [77][78][79][80].…”

Molecular‐targeted agents combination therapy for cancer: Developments and potentials

“…In comparison, the antitumor efficacies of coadministration of cytotoxic drugs with PI3K/Akt/mTOR pathway inhibitors have been evaluated more in both clinical and preclinical studies. The PI3K inhibitor GDC‐0941 combined with docetaxel or gemcitabine has been shown to be synergistic in more than 20 tumor cell lines of different origin, and the combination effects were repeatable in vivo . Another study showed that inhibition of the PI3K/Akt pathway by wortmannin markedly potentiated fludarabine‐induced leukemic cell apoptosis, suggesting that combining fludarabine with inhibitors of the PI3K/Akt/mTOR pathway may represent a novel therapeutic strategy for hematological malignancies .…”

“…The PI3K inhibitor GDC-0941 combined with docetaxel or gemcitabine has been shown to be synergistic in more than 20 tumor cell lines of different origin, and the combination effects were repeatable in vivo. 49 Another study showed that inhibition of the PI3K/Akt pathway by wortmannin markedly potentiated fludarabine-induced leukemic cell apoptosis, suggesting that combining fludarabine with inhibitors of the PI3K/Akt/mTOR pathway may represent a novel therapeutic strategy for hematological malignancies. 50 In clinical trials, the mTOR inhibitors ridaforolimus and everolimus have been combined with agents like paclitaxel, capecitabine or octreotide.…”