Multicenter Phase II Trial of the WEE1 Inhibitor Adavosertib in Refractory Solid Tumors Harboring

PURPOSE: Preclinical cancer models harboring PATIENTS AND METHODS: Patients aged ≥ 18 years with measurable disease and refractory solid tumors harboring RESULTS: Thirty patients were enrolled. The median follow-up duration was 9.9 months. Eight patients had partial responses (PRs), and three had stable disease (SD) ≥ 6 months, with an ORR of 27% (95% CI, 12 to 46), a SD ≥ 6 months/PR rate of 37% (95% CI, 20 to 56), a median progression-free survival duration of 4.1 months (95% CI, 1.8 to 6.4), and a median overall survival duration of 9.9 months (95% CI, 4.8 to 15). Fourteen patients with epithelial ovarian cancer showed an ORR of 36% (95% CI, 13 to 65) and SD ≥ 6 months/PR of 57% (95% CI, 29 to 82), a median progression-free survival duration of 6.3 months (95% CI, 2.4 to 10.2), and a median overall survival duration of 14.9 months (95% CI, 8.9 to 20.9). Common treatment-related toxicities were GI, hematologic toxicities, and fatigue. CONCLUSION: Adavosertib monotherapy demonstrates a manageable toxicity profile and promising clinical activity in refractory solid tumors harborin

Linking the northern Alps with their foreland: The latest exhumation history resolved by low-temperature thermochronology

The evolution of the Central Alpine deformation front (Subalpine Molasse) and its undeformed foreland is recently debated because of their role for deciphering the late orogenic evolution of the Alps. Its latest exhumation history is poorly understood due to the lack of late Miocene to Pliocene sediments. We constrain the late Miocene to Pliocene history of this transitional zone with apatite fission track and (U-Th)/He data. We used laser ablation inductively coupled mass spectrometry for apatite fission track dating and compare this method with previously published and unpublished external detector method fission track data. Two investigated sections across tectonic slices show that the Subalpine Molasse was tectonically active after the onset of folding of the Jura Mountains. This is much younger than hitherto assumed. Thrusting occurred at 10, 8, 6–5 Ma and potentially thereafter. This is contemporaneous with reported exhumation of the External Crystalline Massifs in the central Alps. The Jura Mountains and the Subalpine Molasse used the same detachments as the External Crystalline Massifs and are therefore kinematically coupled. Estimates on the amount of shortening and thrust displacement corroborate this idea. We argue that the tectonic signal is related to active shortening during the late stage of orogenesis

Nudel and FAK as Antagonizing Strength Modulators of Nascent Adhesions through Paxillin

Competition for binding to the cellular protein paxillin by the proteins Nudel and focal adhesion kinase is important for the proper regulation of cell adhesion and migration