Looking for a new panacea in ALK-rearranged NSCLC: may be Ceritinib?

In the past decade, the advent of targeted therapy led to a silent revolution in the war against lung cancer and a significant evolution on the concept of Phase I clinical trials design. Thanks to the specificity of their target, the new drugs have radically changed NSCLC treatment, leading to the development of personalized strategies. The accelerated approval of the first ALK-inhibitor, Crizotinib and more recently Ceritinib, without a Phase III randomized, clinical trial, has been an amazing success story in lung cancer research, marking the beginning of a new decade of targeted drugs development, characterized by modern, biomarker-driven, early clinical trial design and shorter times for clinical approval. Is Ceritinib a new panacea for the treatment of ALK-rearranged NSCLC? We aimed to discuss the reasons of such success, including the new emerging questions, regarding mechanisms of acquired resistance, and the best treatment algorithm for ALK-rearranged NSCLC patients

Zircon u-pb dating and petrogenesis of multiple episodes of anatexis in the north dabie complex zone, central china

The North Dabie complex zone (NDZ), central China, is a high-T ultrahigh-pressure (UHP) metamorphic terrane. It underwent a complex evolution comprising of multistage metamorphism and multiple anatectic events during the Mesozoic continental collision, characterized by granulite-facies overprinting and a variety of migmatites with different generations of leucosomes. In this contribution, we carried out an integrated study including field investigation, petrographic observations, zircon U-Pb dating, and whole-rock element and Sr-Nd-Pb isotope analysis for the migmatites in the NDZ and their leucosomes and melanosomes. As a result, four groups of leucosomes have been recognized: Group 1 (garnet-bearing leucosome), strongly deformed leucosomes with coarse-grained peritectic garnet; Group 2 (amphibole-rich leucosome), weakly deformed to undeformed amphibole-rich leucosomes with coarse-grained peritectic amphibole and no garnet; Group 3 (amphibole-poor leucosome), weakly deformed to undeformed amphibole-poor leucosomes with minor fine-grained amphibole; Group 4 (K-feldspar-rich leucosome), K-feldspar-rich leucosomes mainly composed of coarse-grained quartz, plagioclase and K-feldspar. Zircon SHRIMP and LA-ICPMS U-Pb dating suggest that the Group 1 leucosomes formed at 209 ± 2 Ma whereas the rest of the leucosome groups (Groups 2–4) occurred between 145–110 Ma, in response to decompression under granulite-facies conditions during the early stage of exhumation, and to heating during post-orogenic collapse, respectively. Furthermore, the garnet-bearing leucosomes were resulted from fluid-absent anatexis related to biotite dehydration melting, while the other three groups of leucosomes were formed during large-scale fluid-present partial melting and coeval migmatization. This migmatization comes from heating from the mountain-root removal and asthenosphere upwelling, together with the influx of fluids derived from country rocks at mid-upper crustal levels. However, all the leucosomes and melanosomes display Pb-isotopic compositions similar to those observed for the NDZ UHP rocks (eclogites and granitic gneisses), suggesting a common source from the Triassic subducted Neoproterozoic lower-crustal rocks. In addition, the Cretaceous partial melting and migmatization began at 143 ± 2 Ma with three age-peaks at 133 ± 3 Ma, 124 ± 3 Ma and 114 ± 7 Ma, respectively