The distinctive nature of adenocarcinoma of the lung

Giandomenico RovielloDepartment of Molecular and Translational Medicine, University of Brescia, Brescia, ItalyAbstract: In recent years, many personalized treatments have been developed for NSCLC (non-small-cell lung cancer) patients. Among these, gefitinib, erlotinib, and afatinib are selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors for patients with EGFR gene mutations, while crizotinib and ceritinib are two new tyrosine kinase inhibitors directed against the echinoderm microtubule-like protein 4-anaplastic lymphoma kinase translocation. The possibility of these new molecules being used to treat patients without adenocarcinoma histology is notably small. For example, EGFR mutations and anaplastic lymphoma kinase fusion gene rearrangement are rare in patients with squamous cell carcinoma (generally <1%). Additionally, the benefit of targeted treatment approaches in patients with small-cell lung cancer histology is limited. All of these findings highlight the distinctive nature of adenocarcinoma of the lung among all lung cancer subtypes. Unfortunately, to date, less than 15% of patients with adenocarcinoma of the lung are ideal candidates for these targeted therapies.Keywords: lung cancer, adenocarcinoma, EGFR, AL

New-Generation Hormone Therapies in Nonmetastatic Castration-Resistant Prostate Cancer: Why, Who, When

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Geopolymer composites for potential applications in cultural heritage

A new class of geopolymer composites, as materials alternative to traditional binders, was synthesized and its potentialities as restoration material in Cultural Heritage has been explored. This material has been prepared through a co-reticulation reaction in mild conditions of a metakaolin-based geopolymer inorganic matrix and a commercial epoxy resin. The freshly prepared slurry displays a consistency, workability and thixotropic behavior that make it suitable to be spread on different substrates in restoration, repair and reinforcement actions, even on walls and ceilings. Applicability and compatibility tests on tuff and concrete substrates were carried out and the microstructure of the samples in correspondence of the transition zone was analyzed by means of scanning electron microscope (SEM) observations and energy dispersive spectroscopy (EDS) mapping. Our studies pointed out the formation of a continuous phase between the geopolymer composite and tuff and concrete substrates, highlighting a high compatibility of the geopolymer binder with different kinds of materials. These features indicate a large potential for applications of these materials in Cultural Heritage

Is there still a place for docetaxel rechallenge in prostate cancer?

Three-weekly docetaxel plus prednisone is the standard first-line cytotoxic treatment for patients with metastatic castrate-resistant prostate cancer (mCRPC). Today, several new treatment options are available for patients with tumor progression after first-line docetaxel: Abiraterone, enzalutamide, cabazitaxel, sipuleucel-T immunotherapy, and the radionuclide radium-223. However, despite the evolving scenario in CRPC treatment, the optimal sequencing of the innovative therapies remains unclear. The reintroduction of docetaxel at the occurrence of disease progression after a drug holiday (docetaxel rechallenge) was often proposed, and this chemotherapeutic agent showed to maintain antitumor activity in mCRPC patients. Docetaxel rechallenge may still constitute a valid treatment option mainly for patients with favorable response to first-line docetaxel, at least > 3 mo progression-free interval, age less than 75 years, good performance status, and acceptable docetaxel toxicity. The risk of cumulative toxicity must be evaluated, since sensory neuropathy, nail disorders and fatigue might occur on docetaxel rechallenge

The combination of bevacizumab with chemotherapy is more beneficial in the metastatic setting rather than in the adjuvant setting for the treatment of HER2-negative breast cancer—a commentary on the E5103 randomized phase III clinical study

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Optimal primary end point in Phase II trials of immune checkpoint inhibitors for advanced solid cancers: An evolving issue

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Results from a meta-analysis of immune checkpoint inhibitors in first-line renal cancer patients: does PD-L1 matter?

Background: The aim of this study was to perform a literature-based meta-analysis to assess the efficacy of the novel immune checkpoint inhibitors (ICIs) in first-line metastatic renal cell carcinoma (RCC), focusing on the predictive role of PD-L1 expression. Methods: The primary outcome was overall survival, and secondary outcomes were progression-free survival (PFS) and objective response. We planned a subgroup analysis for overall survival according to PD-L1 status. Results: Five studies were included in the analysis for a total of 4063 cases. Overall survival was greater in PD-L1 positive tumours (HR = 0.49, 95% CI: 0.36\u20130.67; p < 0.001). The pooled analysis of the unselected cases showed a statistically significative improvement in PFS with the use of ICIs (HR = 0.85, 95% CI: 0.72\u20130.99; p = 0.04) and we found a greater PFS benefit (HR = 0.65, 95% CI: 0.57\u20130.74; p < 0.001) in patients with PD-L1 positive tumours. Conclusions: This study supports the efficacy of ICIs and, although a significant clinical benefit has been reported in PD-L1 negative patients, a greater efficacy of ICIs was observed in PD-L1 positive patients. More prospective randomized studies are needed to clarify the role of PDL-1 status in metastatic RCC treated with ICIs

Synthesis of highly regioregular poly[3-(4-alkoxyphenyl)-thiophene]s by oxidative catalysis using copper complexes

A novel, easy, and cost-effective synthetic procedure is reported for the production of very highly regioregular poly[3-(4-alkoxyphenyl)thiophene]s by means of oxidative coupling. Four copper complexes were synthesized and used as catalysts to obtain polymers with higher regioregularity compared to the previous oxidative coupling methodologies reported in the literature and similar to that obtained by McCullough and Rieke methods in the synthesis of poly-3-alkylthiophenes. The regioregularity of the synthesized polymers was investigated by UV-Visible characterization on polymer thin films and 1H NMR analysis. The remarkable potentialities of these polymers have emerged from field-effect transistor mobility measurements operated on devices with bottom-contact configuration and hexamethyldisilazane-treated SiO 2 gate dielectric, showing a well-defined p-type field-effect response and maximum mobility values in air higher than 10-4 cm 2 V-1 s-1. © 2013 Wiley Periodicals, Inc