Michelle Nannini

TL;DR: GDC-0068 is a highly selective, orally bioavailable Akt kinase inhibitor that shows pharmacodynamic inhibition of Akt signaling and robust antitumor activity in human cancer cells in vitro and in vivo.

TL;DR: Comparisons with corresponding clinical trials indicate that these state-of-the-art, mutant Kras-driven GEMMs model human responses well, and lay the foundation for the use of validated GEMM in predicting outcome and interrogating mechanisms of therapeutic response and resistance.

TL;DR: By lowering the intrinsic clearance, a set of imidazobenzoxazepin compounds are derived that showed improved unbound drug exposure and effectively suppressed growth of tumors in a mouse xenograft model at low drug dose levels.

TL;DR: Potent inhibition of AKT signaling with ipatasertib was associated with a tolerable safety profile and meaningful disease control in a subgroup of patients, and Targeting pAKT with an ATP-competitive inhibitor provides a greater therapeutic window than allosteric inhibitors.

TL;DR: The potent efficacy of SU11248 in models representing diverse signaling paradigms results from simultaneous inhibition of individual target receptors expressed both in cancer cells and in the tumor neovasculature, supporting the hypothesis that multitargeted inhibitors have the cumulative antitumor efficacy of combined single-target inhibitors.