Marion Dorsch

TL;DR: By identifying a drug combination that delays or even combats development of resistance when used as a first-line treatment in clinical trials, these results could ultimately improve the lives of patients with medulloblastoma or other cancers that depend on Smo for their survival.

TL;DR: The biologic characterization of the 2-morpholino pyrimidine derivative pan-PI3K inhibitor NVP-BKM120 shows dose-dependent in vivo pharmacodynamic activity as measured by significant inhibition of p-Akt and tumor growth inhibition in mechanistic xenograft models and behaves synergistically when combined with either targeted agentssuch as MEK or HER2 inhibitors or with cytotoxic agents such as docetaxel or temozolomide.

TL;DR: A primary xenograft model of small-cell lung cancer is described in which endobronchial tumor specimens obtained from chemo-naive patients are serially propagated in vivo in immunodeficient mice to identify a group of tumor-specific genes expressed in primary SCLC and Xenografts that was lost during the transition to tissue culture and that was not regained when the tumors were reestablished as secondary xenografteds.

TL;DR: This study provides molecular insights that help explain the heterogeneous response of KRAS mutant cancers to MEK pathway inhibition and presents a strong rationale for the clinical testing of combination MEK and PI3K targeted therapies.

TL;DR: Structural-activity relationship studies led to the discovery of a potent and specific Smoothened antagonist N-(6-((2S,6R)-2,6-dimethylmorpholino)pyridin-3-yl)-2-methyl-4'-(trifluoromethoxy)biphenyl- 3-carboxamide (5m, NVP-LDE225), which is currently in clinical development.