Targeting the KRAS Pathway in Non-Small Cell Lung Cancer.

: Lung cancer remains the leading cause of cancer-related deaths worldwide. However, significant progress has been made individualizing therapy based on molecular aberrations (e.g., EGFR, ALK) and pathologic subtype. KRAS is one of the most frequently mutated genes in non-small cell lung cancer (NSCLC), found in approximately 30% of lung adenocarcinomas, and is thus an appealing target for new therapies. Although no targeted therapy has yet been approved for the treatment of KRAS-mutant NSCLC, there are multiple potential therapeutic approaches. These may include direct inhibition of KRAS protein, inhibition of KRAS regulators, alteration of KRAS membrane localization, and inhibition of effector molecules downstream of mutant KRAS. This article provides an overview of the KRAS pathway in lung cancer and related therapeutic strategies under investigation. IMPLICATIONS FOR PRACTICE: The identification of oncogene-addicted cancers and specific inhibitors has revolutionized non-small cell lung cancer (NSCLC) treatment and outcomes. One of the most commonly mutated genes in adenocarcinoma is KRAS, found in approximately 30% of lung adenocarcinomas, and thus it is an appealing target for new therapies. This review provides an overview of the KRAS pathway and related targeted therapies under investigation in NSCLC. Some of these agents may play a key role in KRAS-mutant NSCLC treatment in the future.

UV light promoted 'Metal'/'Additive'-free oxidation of alcohols: investigating the role of alcohols as electron donors.

UV light promoted selective oxidation of primary and secondary alcohols has been demonstrated under 'metal-free' and 'additive-free' conditions. Under the optimized conditions, a variety of aromatic, heteroaromatic, and alicyclic alcohols have been examined for their transformations to the corresponding carbonyl compounds. The mechanistic studies emphasize the important role of substrate (alcohol) and solvent (DMSO) in the generation of superoxide radical which is a vital intermediate for the transformation. This study also highlights the role of air as the oxidant in the oxidation process. Further, the practical application of the strategy has also been demonstrated for the oxidation of the alcoholic moiety in cholesterol.

Encapsulating Au-Fe3 O4 Nanodots into AIE-active Supramolecular Assemblies: Ambient Visible-light Harvesting "Dip-Strip" Photocatalyst for C-C/C-N Bond Formation Reactions.

The present study demonstrates the development of a supramolecular porous ensemble consisting of hetero-oligophenylene derivative 6 and Au-Fe3 O4 nanodots. Supramolecular assemblies of AIE-active hetero-oligophenylene derivative 6 served as reactors for the generation of Au-Fe3 O4 nanodots. The as prepared supramolecular ensemble functioned as an efficient recyclable photocatalytic system for C(sp2 )-H bond activation of anilines for the construction of quinoline carboxylates. Interestingly, the "dip catalyst" prepared by depositing PTh-co-PANI-6: Au-Fe3 O4 nanodots on a filter paper served as a recyclable strip (up to 10 cycles) for C-C/C-N bond formation reaction.

Empowering Transition-Metal-Free Cascade Protocol for the Green Synthesis of Biaryls and Alkynes.

The work being presented in this paper demonstrates the simple and efficient "transition-metal-free" and "light-mediated" synthetic protocol for the synthesis of aryl iodides/biaryls/alkynes from aryl bromides. Under ultraviolet irradiation and in basic aqueous media, aryl bromides undergo transformation into aryl iodides which efficiently couple via a cascade reaction with a wide range of terminal alkynes/unactivated arenes to generate target molecules under green conditions.

Correlation of Neutrophil to Lymphocyte Ratio and Absolute Neutrophil Count With Outcomes With PD-1 Axis Inhibitors in Patients With Advanced Non-Small-Cell Lung Cancer.

INTRODUCTION: Programmed death-1 (PD-1) axis inhibitors have become standard therapy in advanced non-small-cell lung cancer (NSCLC). Response might be delayed and pseudo-progression occasionally occurs in patients who eventually benefit from treatment. Additional markers beyond programmed death ligand 1 (PD-L1) expression are needed to assist in patient selection, response evaluation, and treatment decisions. MATERIALS AND METHODS: The relationship between prospectively collected clinical outcomes (response, disease control rate [DCR], treatment duration, overall survival) and hematologic parameters (neutrophil to lymphocyte ratio [NLR], absolute neutrophil count [ANC], and platelet to lymphocyte ratio [PLR]) was explored retrospectively in advanced NSCLC patients treated with PD-1 axis inhibitors at a major cancer center from May 2013 to August 2016. Hematologic parameters at baseline and during treatment (week 2 or 3 and week 8) were included. RESULTS: Of 88 patients treated with PD-1 axis inhibitors, 22 (25%) experienced partial response. Baseline NLR ≤4 was associated with superior DCR (74% vs. 50%; P = .025), treatment duration (P = .037), time to progression (P = .053), and overall survival (P = .019), with no differential association according to PD-L1 tumor expression. Lower NLR and ANC during treatment were also associated with response to treatment (P = .025 and P = .017, respectively), and treatment duration (P = .036 and P = .008). No association was found between baseline PLR and DCR, response, treatment duration, nor overall survival. CONCLUSION: Baseline NLR ≤4 and lower NLR and ANC during treatment might correlate with disease control and treatment response and should be explored further as potential predictors of treatment benefit in larger studies.

Aggregates of a hetero-oligophenylene derivative as reactors for the generation of palladium nanoparticles: a potential catalyst in the Sonogashira coupling reaction under aerial conditions.

The utilization of Pd nanoparticles stabilized by aggregates of hetero-oligophenylene derivative 3 as an excellent catalyst in a copper/amine free Sonogashira coupling reaction under aerial conditions at room temperature has been demonstrated.