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- W2012080598 abstract "Abstract #3125 Background: Rapamycin inhibits downstream signals from the mammalian target of rapamycin (mTOR), a known kinase member of a signaling pathway that promotes tumor growth. Rapamycin9s poor aqueous solubility and poor chemical stability have limited its development as an intravenous (IV) anticancer agent. Nab -rapamycin utilizes the albumin-bound technology to allow for IV administration of rapamycin and has demonstrated dose-linear pharmacokinetics and safety up to 90 mg/kg with effective antitumor activity at 40 mg/kg against a human panel of tumor xenografts. This study investigated the efficacy of combined therapy with nab -paclitaxel (Abraxane®) utilizing invasive human breast (MDA-MB-231) and colon (HT29) cancer xenograft models. Material and Methods: Xenograft transplants using luciferase-tagged MDA-MB-231 cells were implanted into mammary fatpad of SCID mice and allowed to reach 460 mm 3 in size prior to IV administration of saline (vehicle, n = 9); nab -rapamycin, 3x wkly for 2 wks at 40 mg/kg ( nab -rap-2W; n = 8); nab -rapamycin, 3x wkly for 4 wks at 40 mg/kg ( nab -rap-4W; n = 8); Abraxane, qdx5 at 30 mg/kg (ABX; n = 8); nab -rap-2W + ABX (n = 9); or nab -rap-4W + ABX (n = 8). HT29 xenografts were also treated with nab -rap-4W (n = 8) and nab -rap-4W + ABX (10 mg/kg, qdx5, IP, n = 8). The in vivo antiangiogenic effect of nab -rapamycin was evaluated using the standard in vivo chick chorioallantoic membrane (CAM) assay with 3-day old embryos (n = 18). Results: Relative to vehicle controls, nab -rap-2W ( P nab -rap-4W ( P P nab -rapamycin + ABX with TGI of 81% and 86% for nab -rap-2W + ABX and nab -rap-4W + ABX groups, respectively. For HT29 tumors, the combination of ABX and nab -rapamycin also showed greater TGI (89%) compared to nab -rapamycin alone (81%). In the chick CAM assay, nab -rapamycin demonstrated antiangiogenic efficacy at doses of 10 µg and above without affecting embryo viability. Conclusions: Combination therapy of nab -rapamycin and Abraxane was more effective at inhibiting breast and colon xenograft tumor growth than single therapy of either drug. The enhanced antitumor activity seen with combined nab -rapamycin-Abraxane may in part be due to the observed antiangiogenic activity of nab -rapamycin. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3125." @default.
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- W2012080598 date "2009-01-15" @default.
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- W2012080598 title "Antitumor activity, and antiangiogenic activity of nanoparticle albumin-boundnab-rapamycin in combination withnab-paclitaxel." @default.
- W2012080598 doi "https://doi.org/10.1158/0008-5472.sabcs-3125" @default.
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