Lung Cancer Treatments and Mutations

EML4-ALK Fusion Rewires Transcriptomic, miRNA, and CAF-Associated Programs in Non-Small Cell Lung Cancer

This paper identifies transcriptomic, miRNA, and CAF-associated reprogramming in EML4-ALK fusion-positive NSCLC compared to fusion-negative tumors.

Overcoming EGFR resistance by monovalent and bident inhibitors targeting Cys775

This paper develops covalent EGFR inhibitors targeting cysteine 775 and 797, showing improved efficacy and resistance delay in osimertinib-resistant models.

M1C is a druggable target for NSCLC KRAS G12C mutant tumors resistant to KRAS inhibitors

This study identifies M1C as a driver of sotorasib resistance in NSCLC KRAS G12C mutant tumors and shows that targeting M1C improves treatment outcomes.

SMARCA4, STK11, and KEAP1 co-inactivation associates with poor prognosis and upregulation of the TGF-β pathway in lung adenocarcinoma

The paper identifies SMARCA4/STK11/KEAP1 triple mutant lung adenocarcinoma as a poor prognosis subset and links it to TGF-β pathway activation.

Peristromal niches protect lung cancers from targeted therapies through a combined effect of multiple molecular mediators

This study shows that stromal niches protect lung cancers from ALK inhibitors through multiple mechanisms, and targeting these mechanisms together is more effective than targeting them individually.

Adaptive regulation of dNTP homeostasis confers osimertinib resistance in EGFR mutant non-small cell lung carcinoma

This study identifies dNTP homeostasis regulation as a mechanism of osimertinib resistance in EGFR-mutant NSCLC, revealing therapeutic targets through two regulatory axes.

Modeling acquired TKI resistance and effective combination therapeutic strategies in murine RET+ lung adenocarcinoma

This study models acquired resistance to RET inhibitors in murine lung cancer and identifies combination therapies that improve treatment outcomes.

NEK7 phosphorylation of cortactin modulates the migratory capacity of cells expressing EML4-ALK V3

This study identifies NEK7-mediated phosphorylation of cortactin as a mechanism by which EML4-ALK V3 enhances cell migration through actin cytoskeleton remodeling.

RRAS and RRAS2 mutations are recurrent oncogenic drivers in lung cancer and are sensitive to the pan-RAS inhibitor RMC-6236

This study identifies RRASQ87L and RRAS2Q72L mutations as recurrent oncogenic drivers in lung cancer and shows sensitivity to the pan-RAS inhibitor RMC-6236.

Cancer-associated fibroblasts confer ALK inhibitor resistance in EML4-ALK-driven lung cancer via concurrent integrin and MET signaling

This study identifies that CAFs confer ALK inhibitor resistance in EML4-ALK-driven lung cancer through both MET and integrin signaling pathways, and shows that targeting both pathways improves treatment efficacy.

Dual targeting of RET and SRC synergizes in RET fusion-positive cancer cells

This study shows that combining RET and SRC inhibitors enhances anti-cancer effects in RET fusion-positive cancers by suppressing PAK signaling and restoring sensitivity in resistant cells.

Transcriptional program-based deciphering of the MET exon 14 skipping regulation network

The paper identifies a regulatory network involving ETS1, FOSL1, and SMAD3 that mediates MET exon 14 skipping in lung cancer, showing their role in RAS-ERK pathway activation and potential as therapeutic targets.

EML4-ALK variant-specific genetic interactions shape lung tumorigenesis

The paper investigates functional differences between EML4-ALK variants V1 and V3 in lung cancer using mouse models and human data, showing variant-specific effects on tumorigenesis.

Deep Mutational Scanning Reveals EGFR Mutations Conferring Resistance to the 4th-generation EGFR tyrosine kinase inhibitor BLU-945

This study identifies EGFR mutations conferring resistance to BLU-945 using deep mutational scanning and shows that combination treatment may suppress resistance mechanisms.

Phenotypic plasticity in a novel set of EGFR tyrosine kinase inhibitor-adapted non-small cell lung cancer cell lines

This study characterizes phenotypic plasticity in EGFR inhibitor-resistant NSCLC cell lines, showing diverse resistance mechanisms and metabolic adaptations across sublines.

Mapping kinase domain resistance mechanisms for the MET receptor tyrosine kinase via deep mutational scanning

The paper uses deep mutational scanning to analyze MET kinase domain mutations and their resistance to 11 inhibitors, identifying resistance and sensitizing mutations and improving prediction with a protein language model.

Single-cell multi-omics reveals tumor microenvironment factors underlying poor immunotherapy responses in ALK-positive lung cancer

The paper uses single-cell multi-omics to identify immunosuppressive factors in ALK-positive lung cancer that contribute to poor immunotherapy responses.

A Molecular Dynamics Protocol for Rapid Prediction of EGFR Overactivation and Its Application to the Rare Mutations S768I, S768N, D761N

This paper develops a molecular dynamics protocol to predict EGFR mutation effects and applies it to three rare mutations, showing how they alter structural dynamics and activity.

Conserved regulatory motifs in the juxtamembrane domain and kinase N-lobe revealed through deep mutational scanning of the MET receptor tyrosine kinase domain.

Retrospective study on the clinicogenomic characteristics of EGFR mutant and wildtype NSCLC

This study compares clinicogenomic features of EGFR mutant and wildtype NSCLC using public data, finding differences in demographics, metastasis patterns, survival, and mutational landscapes.

SMARCA4 Mutations in KRAS-mutant Lung Adenocarcinoma: A Multi-cohort Analysis

This study analyzes SMARCA4 mutations in KRAS-mutant lung adenocarcinoma across multiple cohorts, finding adverse clinical outcomes associated with SMARCA4 mutations in both non-immunotherapy and immunotherapy-treated patients.

High frequency of Exon 20 S768I EGFR mutation detected in malignant pleural effusions: a poor prognosticator of NSCLC?

The paper detects a high frequency of S768I EGFR mutation in malignant pleural effusions and links it to poor prognosis in NSCLC.

Molecular subtyping and prognostic assessment based on tumor mutation burden in patients with lung adenocarcinomas

The paper identifies two molecular subtypes of lung adenocarcinomas based on tumor mutation burden and links them to clinical and genomic differences.

Systems therapeutics analyses identify genomic signatures defining responsiveness to allopurinol and combination therapy for lung cancer

The paper identifies genomic signatures predicting allopurinol and combination therapy responses in lung cancer using TCGA, CCLE, and patient-derived tumor data.