ArticleScience translational medicine2019
Development of combination therapies to maximize the impact of KRAS-G12C inhibitors in lung cancer.
Article in Science translational medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 134 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
134 citing papers in PubMed, 1 synthesis or guideline pooled it, 220 citations in OpenAlex.
- Current status of KRAS G12C inhibitors in NSCLC and the potential for combination with anti-PD-(L)1 therapy: a systematic review.Frontiers in immunology · 2025Pooled it
- Review
- Increased mRNA translation delays tumour initiation and exposes a therapeutic vulnerability in lung cancer.Molecular cancer · 2026Article
- Targeting the NF-κB pathway represents a potential strategy to attenuate HGF-induced resistance to KRAS G12C inhibitors in lung adenocarcinoma.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Article
- Discovery and Characterization of Divarasib (GDC-6036), a Potent Covalent Inhibitor of KRAS G12C.Journal of medicinal chemistry · 2026Article
- The GENEVA platform models tumor mosaicism to reveal variations of responses to KRAS inhibitors and identify improved drug combinations.Nature cancer · 2026Article
- Tumor immune microenvironment facilitates resistance to KRAS G12C inhibitor sotorasib by altered PD-L1 expression.Journal for immunotherapy of cancer · 2026Article
- CRISPR knockout screens reveal JUN as the master mediator of resistance to MAPK inhibition in KRAS-mutant pancreatic cancer.Journal of experimental & clinical cancer research : CR · 2026Article
- IGF-1R inhibitors in cancer: A review of available evidence and future outlook.Critical reviews in oncology/hematology · 2025Review
- Orthotopically Implanted Murine Lung Adenocarcinoma Cell Lines for Preclinical Investigations.Cancers · 2025Review
- RETRACTED: The Impact ofInternational journal of molecular sciences · 2025Review
- KRAS mutated NSCLC: past, present, and future directions in a rapidly evolving landscape.The oncologist · 2025Review
- Efficacy and toxicity of stereotactic radiotherapy combined with third-generation EGFR-TKIs and immunotherapy in patients with brain metastases from non-small cell lung cancer.Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al] · 2025Article
- Dual inhibition of GTP-bound KRAS and mTOR in lung adenocarcinoma and squamous cell carcinoma harboring KRAS G12C.Cell communication and signaling : CCS · 2025Article
- Tumor-Infiltrating Clonal Hematopoiesis.The New England journal of medicine · 2025Article
- Enhancing KRAS G12D inhibitor sensitivity in pancreatic cancer through SHP2/PI3K pathway.Medical oncology (Northwood, London, England) · 2025Article
- A Pan-RAS Inhibitor with a Unique Mechanism of Action Blocks Tumor Growth and Induces Antitumor Immunity in Gastrointestinal Cancer.Cancer research · 2025Article
- Lung cancer immunotherapy in 2025: where we stand and what comes next?Frontiers in immunology · 2025Review
- Therapeutic strategies for KRAS G12C-mutant non-small cell lung cancer: from bench to bedside and beyond.Frontiers in pharmacology · 2025Review
- Article
74 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
KRAS represents an excellent therapeutic target in lung cancer, the most commonly mutated form of which can now be blocked using KRAS-G12C mutant-specific inhibitory trial drugs. Lung adenocarcinoma cells harboring KRAS mutations have been shown previously to be selectively sensitive to inhibition of mitogen-activated protein kinase kinase (MEK) and insulin-like growth factor 1 receptor (IGF1R) signaling. Here, we show that this effect is markedly enhanced by simultaneous inhibition of mammalian target of rapamycin (mTOR) while maintaining selectivity for the KRAS-mutant genotype. Combined mTOR, IGF1R, and MEK inhibition inhibits the principal signaling pathways required for the survival of KRAS-mutant cells and produces marked tumor regression in three different KRAS-driven lung cancer mouse models. Replacing the MEK inhibitor with the mutant-specific KRAS-G12C inhibitor ARS-1620 in these combinations is associated with greater efficacy, specificity, and tolerability. Adding mTOR and IGF1R inhibitors to ARS-1620 greatly improves its effectiveness on KRAS-G12C mutant lung cancer cells in vitro and in mouse models. This provides a rationale for the design of combination treatments to enhance the impact of the KRAS-G12C inhibitors, which are now entering clinical trials.
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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.