ArticleCancer discovery2024
Alveolar Differentiation Drives Resistance to KRAS Inhibition in Lung Adenocarcinoma.
Article in Cancer discovery, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
50 citing papers in PubMed, 57 citations in OpenAlex.
- The Role of KRAS in Non-Small Cell Lung Cancer: From Molecular Background to Precision Medicine.International journal of molecular sciences · 2026Review
- Single-cell-marker-based subtyping and multi-level analyses uncover the prognostic effects, dysregulations and therapeutic indicative potential of an eight-gene signature in lung adenocarcinoma.Cancer cell international · 2026Article
- Mevalonate pathway rewiring driven by enhancer remodelling confers resistance to KRAS inhibitors in colorectal cancer.Nature communications · 2026Article
- A Roadmap to Transform Lung Cancer Outcomes: Priorities in Biology, Therapeutic Innovation, Early Detection, Prevention, and Interception.Cancer discovery · 2026Review
- RAS pathway activity subtypes identified by machine learning define prognostic and immune microenvironment characteristics in lung adenocarcinoma.Discover oncology · 2026Article
- GLIS3 marks a neural-like progenitor cell state that drives metastasis in pancreatic ductal adenocarcinoma.Cell reports · 2026Article
- Article
- Article
- Unlocking Alveolar Regeneration: AT2 Stem Cells, Signaling Networks, and Therapeutic Frontiers.Stem cell reviews and reports · 2026Review
- KRAS and MYC synergistic inhibition: a powerful strategy targeting KRAS-mutant cancers.Molecular cancer · 2026Review
- Mitotic spindle-organizing protein 2A (MZT2A) promotes cisplatin resistance through NEMO ubiquitination and NF-κB activation in lung adenocarcinoma.The Journal of biological chemistry · 2026Article
- Tolerance and Resistance to Targeted Therapy in NSCLC: Emerging Concepts and Strategies.JTO clinical and research reports · 2026Review
- UnlockingCurrent oncology (Toronto, Ont.) · 2026Review
- Article
- Deep-Learning Tool ScVital Enables Species-Agnostic Integration of Cancer Cell States.Cancer research · 2026Article
- A Plastic EMP1+ to LGR5+ Cell State Conversion as a Bypass to KRASG12D Pharmacologic Inhibition in Metastatic Colorectal Cancer.Cancer discovery · 2026Article
- Kras G12C- and G12D-driven lung cancers differ in oncogenic potency, immunogenicity, and relapse after Kras inhibition in mouse models.Science translational medicine · 2026Article
- Oncogenic KRAS/ERK/JUNB signaling suppresses differentiation regulator GATA6 in pancreatic cancer.The Journal of clinical investigation · 2026Article
- Paneth-like transition drives resistance to dual targeting of KRAS and EGFR in colorectal cancer.Cancer cell · 2026Article
- Article
Corrections and comments
- Update of
Authors and funding
17 authors at 4 institutions in 3 countries.
Funding
Abstract
Lung adenocarcinoma (LUAD), commonly driven by KRAS mutations, is responsible for 7% of all cancer mortality. The first allele-specific KRAS inhibitors were recently approved in LUAD, but the clinical benefit is limited by intrinsic and acquired resistance. LUAD predominantly arises from alveolar type 2 (AT2) cells, which function as facultative alveolar stem cells by self-renewing and replacing alveolar type 1 (AT1) cells. Using genetically engineered mouse models, patient-derived xenografts, and patient samples, we found inhibition of KRAS promotes transition to a quiescent AT1-like cancer cell state in LUAD tumors. Similarly, suppressing Kras induced AT1 differentiation of wild-type AT2 cells upon lung injury. The AT1-like LUAD cells exhibited high growth and differentiation potential upon treatment cessation, whereas ablation of the AT1-like cells robustly improved treatment response to KRAS inhibitors. Our results uncover an unexpected role for KRAS in promoting intratumoral heterogeneity and suggest that targeting alveolar differentiation may augment KRAS-targeted therapies in LUAD. SIGNIFICANCE: Treatment resistance limits response to KRAS inhibitors in LUAD patients. We find LUAD residual disease following KRAS targeting is composed of AT1-like cancer cells with the capacity to reignite tumorigenesis. Targeting the AT1-like cells augments responses to KRAS inhibition, elucidating a therapeutic strategy to overcome resistance to KRAS-targeted therapy. This article is featured in Selected Articles from This Issue, p. 201.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.