Multieffect Specific Nanovesicles for Homing Resistant Tumors and Overcoming Osimertinib-Acquired Resistance in NSCLC.

Acquired resistance to osimertinib (Osi) remains a major obstacle in the treatment of patients with EGFR-mutant non-small cell lung cancer (NSCLC). AXL elevation is a known key mechanism of Osi-resistance, and therapeutic strategies remain scarce. Emerging evidence reveals that an increased intracellular glutathione (GSH) level induces Osi resistance.

Neutrophil extracellular traps in tumor metabolism and microenvironment.

Neutrophil extracellular traps (NETs) are intricate, web-like formations composed of DNA, histones, and antimicrobial proteins, released by neutrophils. These structures participate in a wide array of physiological and pathological activities, including immune rheumatic diseases and damage to target organs. Recently, the connection between NETs and cancer has garnered significant attention.

Metformin promotes anti-tumor immunity in mutant NSCLC through AXIN1-dependent upregulation of multiple nucleotide metabolites.

Background: Metformin has pleiotropic effects beyond glucose reduction, including tumor inhibition and immune regulation. It enhanced the anti-tumor effects of programmed cell death protein 1 (PD-1) inhibitors in serine/threonine kinase 11 ( mutant non-small cell lung cancer (NSCLC) through an axis inhibition protein 1 (AXIN1)-dependent manner. However, the alterations of tumor metabolism and metabolites upon metformin administration remain unclear.

Mesoporous manganese nanocarrier target delivery metformin for the co-activation STING pathway to overcome immunotherapy resistance.

Targeting the stimulator of interferon genes (STING) pathway is a promising strategy to overcome primary resistance to immune checkpoint inhibitors in non-small cell lung cancer with the STK11 mutation. We previously found metformin enhances the STING pathway and thus promotes immune response. However, its low concentration in tumors limits its clinical use.

Brigatinib, a newly discovered AXL inhibitor, suppresses AXL-mediated acquired resistance to osimertinib in EGFR-mutated non-small cell lung cancer.

In addition to the classical resistance mechanisms, receptor tyrosine-protein kinase AXL is a main mechanism of resistance to third-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) osimertinib in EGFR-mutated non-small cell lung cancer (NSCLC). Developing an effective AXL inhibitor is important to sensitize osimertinib in clinical application. In this study we assessed the efficacy of brigatinib, a second-generation of anaplastic lymphoma kinase (ALK)-TKI, as a novel AXL inhibitor, in overcoming acquired resistance to osimertinib induced by AXL activation.

Sialyltransferase ST3GAL4 confers osimertinib resistance and offers strategies to overcome resistance in non-small cell lung cancer.

The third-generation EGFR-TKI osimertinib is widely used in EGFR-mutated positive non-small cell lung cancer (NSCLC) patients, but drug resistance is inevitable. The currently known mechanisms only explain resistance in a small proportion of patients. For most patients, the mechanism of osimertinib resistance is still unclear, especially for EGFR-independent resistance.

AXIN1/MYC Axis Mediated the Osimertinib Resistance in EGFR Mutant Non-Small Cell Lung Cancer Cells.

Osimertinib, a promising and approved third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), is a standard strategy for EGFR-mutant non-small cell lung cancer (NSCLC) patients. However, developed resistance is unavoidable, which reduces its long-term effectiveness. In this study, RNA sequencing was performed to analyze differentially expressed genes (DEGs).

Overall signature of acquired KRAS gene changes in advanced non-small cell lung cancer patient with EGFR-TKI resistance.

Objective: Numerous scattered case studies continue to demonstrate a strong correlation between acquired KRAS mutations and epidermal growth factor receptor-tyrosine kinase inhibitor resistance in non-small cell lung cancer. However, the comprehensive understanding of the KRAS pathway following the failure of epidermal growth factor receptor-tyrosine kinase inhibitor therapy remains limited.

Methods: We conducted a retrospective evaluation of the next generation sequencing data from 323 patients with advanced non-small cell lung cancer and EGFR-activating mutations after experiencing progression with epidermal growth factor receptor-tyrosine kinase inhibitor therapy.

The potential therapeutic regimen for overcoming resistance to osimertinib due to rare mutations in NSCLC.

The mechanisms of osimertinib resistance have not been well characterized. We conducted next-generation sequencing to recognize novel resistance mechanism and used cell line-derived xenograft (CDX) and patient-derived xenograft (PDX) models to evaluate the anti-proliferative effects of aspirin and . We observed that mutations led to acquired resistance to osimertinib in a patient and further confirmed that both and mutations caused osimertinib resistance.

Pathological Response and Tumor Immune Microenvironment Remodeling Upon Neoadjuvant ALK-TKI Treatment in ALK-Rearranged Non-Small Cell Lung Cancer.

Background: Anaplastic lymphoma kinase-tyrosine kinase inhibitors (ALK-TKI; ALKi) have shown potent antitumor activity in metastatic non-small-cell lung cancer (NSCLC) with ALK rearrangement (ALK+); however, their efficacy in neoadjuvant settings has been poorly explored.

Objective: This retrospective study aimed to examine the clinical activity and tumor immune microenvironment (TIME) changes of neoadjuvant ALKi therapy.

Methods: ALK+ NSCLC patients treated with neoadjuvant ALKi at three hospitals in China between February 2018 and January 2023 were assessed.

Genomic characteristics and prognosis of lung cancer patients with MSI-H: A cohort study.

Background: Microsatellite instability (MSI) is the first pan-cancer biomarker approved to guide immune checkpoint inhibitor therapy for MSI-high (MSI-H) solid tumors. In lung cancer, the MSI-H frequency is very low, and the genetic characteristics and prognosis of lung cancer with MSI-H were rarely reported.

Methods: Next-generation sequencing and immunohistochemistry were used detect MSI status, tumor mutation burden (TMB) and PD-L1 expression.

Electrotaxis of alveolar epithelial cells in direct-current electric fields.

Purpose: This study aims to elucidate the electrotaxis response of alveolar epithelial cells (AECs) in direct-current electric fields (EFs), explore the impact of EFs on the cell fate of AECs, and lay the foundation for future exploitation of EFs for the treatment of acute lung injury.

Methods: AECs were extracted from rat lung tissues using magnetic-activated cell sorting. To elucidate the electrotaxis responses of AECs, different voltages of EFs (0, 50, 100, and 200 mV/mm) were applied to two types of AECs, respectively.

Predictive value of early kinetics of ctDNA combined with cfDNA and serum CEA for EGFR-TKI treatment in advanced non-small cell lung cancer.

Background: Circulating tumor DNA (ctDNA) has made a breakthrough as an early biomarker in operable early-stage cancer patients. However, the function of ctDNA combined with cell-free DNA (cfDNA) as a predictor in advanced non-small cell lung cancer (NSCLC) remains unknown. Here, we explored its potential as a biomarker for predicting the efficacy of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in patients with advanced NSCLC.

pH-responsive theranostic nanoplatform of ferrite and ceria co-engineered nanoparticles for anti-inflammatory.

Multiple component integration to achieve both therapy and diagnosis in a single theranostic nanosystem has aroused great research interest in the medical investigator. This study aimed to construct a novel theranostic nanoplatform ferrite and ceria co-engineered mesoporous silica nanoparticles (Fe/Ce-MSN) antioxidant agent though a facile metal Fe/Ce-codoping approach in the MSN framework. The resulted Fe-incorporated ceria-based MSN nanoparticles possessing a higher Ce-to-Ce ratio than those revealed by ceria-only nanoparticles.

Light-assisted anti-wrinkling on azobenzene-containing polyblend films.

Undesired surface wrinkling is a persistent issue far from being resolved. Here, we report a simple light-assisted strategy to prevent surface wrinkling on azobenzene-containing polyblend films, which is based on the unique photo-responsive behaviors of azobenzene moieties. Upon visible light irradiation, the mechanical strain-induced surface wrinkling of the azo-based polyblend film attached on a pre-strained compliant substrate can be effectively suppressed.

Polarization-Dependent Ultrasensitive Dynamic Wrinkling on Floating Films Induced by Photo-Orientation of Azopolymer.

Ubiquitous surface wrinkling has been well-studied theoretically and experimentally. How to modulate the stress state of a liquid-supported system for the unexploited wrinkling capabilities remains a challenge. Here we report a simple linearly-polarized-light illumination to spatiotemporally trigger ultrasensitive in situ dynamic wrinkling on a floating azo-film.

Protective autophagy decreases lorlatinib cytotoxicity through Foxo3a-dependent inhibition of apoptosis in NSCLC.

Lorlatinib is a promising third-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor (TKI) that has been approved for treating ALK-positive non-small-cell lung cancer (NSCLC) patients with previous ALK-TKI treatment failures. However, the inevitable emergence of acquired resistance limits its long-term efficacy. A more comprehensive understanding of the acquired resistance mechanisms to lorlatinib will enable the development of more efficacious therapeutic strategies.

Metformin Combining PD-1 Inhibitor Enhanced Anti-Tumor Efficacy in Mutant Lung Cancer Through AXIN-1-Dependent Inhibition of STING Ubiquitination.

Non-small-cell lung cancer (NSCLC) with mutation showed primary resistance to immune checkpoint inhibitors (ICIs). The glucose-lowering drug metformin exerted anti-cancer effect and enhanced efficacy of chemotherapy in NSCLC with co-mutation, yet it is unknown whether metformin may enhance ICI efficacy in mutant NSCLC. We studied the impact of metformin on ICI efficacy in mutant NSCLC and using colony formation assay, cell viability assay, Ki67 staining, ELISA, CRISPR/Cas9-mediated knockout, and animal experiments.

Ibrutinib reverses IL-6-induced osimertinib resistance through inhibition of Laminin α5/FAK signaling.

Osimertinib, a 3rd generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), is the first-line standard-of-care for EGFR-mutant non-small cell lung cancer (NSCLC) patients, while acquired drug resistance will inevitably occur. Interleukin-6 (IL-6) is a keystone cytokine in inflammation and cancer, while its role in osimertinib efficacy was unknown. Here we show that clinically, plasma IL-6 level predicts osimertinib efficacy in EGFR mutant NSCLC patients.

Hexokinases II-mediated glycolysis governs susceptibility to crizotinib in ALK-positive non-small cell lung cancer.

Background: Activation of ALK leads to a high level of aerobic glycolysis related to crizotinib insensitivity in anaplastic lymphoma kinase-positive non-small cell lung cancer (ALK NSCLC). The strategy and mechanism of glycolysis inhibition in sensitizing ALK NSCLC cells to crizotinib requires further investigation.

Methods: The levels of glycolysis in H3122 and H2228 cells were evaluated through detection of glucose consumption and lactate production.

Robust Scalable-Manufactured Smart Fabric Surfaces Based on Azobenzene-Containing Maleimide Copolymers for Rewritable Information Storage and Hydrogen Fluoride Visual Sensor.

Functionalized materials with reversible color switching are highly attractive in many application fields, especially as rewritable media for information storage. It is critical yet challenging to develop a cost-effective strategy for the fabrication of stimulus-responsive chromogenic systems. Herein, we present a versatile dip-coating approach to fabricate robust smart textile with acid/base-driven chromotropic capability.

Carbon Nanotubes and Polydopamine Modified Poly(dimethylsiloxane) Sponges for Efficient Oil-Water Separation.

In this paper, effective separation of oil from both immiscible oil-water mixtures and oil-in-water (O/W) emulsions are achieved by using poly(dimethylsiloxane)-based (PDMS-based) composite sponges. A modified hard template method using citric acid monohydrate as the hard template and dissolving it in ethanol is proposed to prepare PDMS sponge composited with carbon nanotubes (CNTs) both in the matrix and the surface. The introduction of CNTs endows the composite sponge with enhanced comprehensive properties including hydrophobicity, absorption capacity, and mechanical strength than the pure PDMS.

VPS34 suppression reverses osimertinib resistance via simultaneously inhibiting glycolysis and autophagy.

Autophagy and glycolysis are associated with osimertinib resistance. The energy complement and dynamic balance between these two processes make it difficult to block the process of drug resistance; breaking the complementary relationship between them may effectively overcome drug resistance. However, the exact mechanisms and the key players for regulating autophagy and glycolysis remain unclear.