ArticleCancer discovery2023
Molecular Characterization of Acquired Resistance to KRASG12C-EGFR Inhibition in Colorectal Cancer.
Article in Cancer discovery, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 98 papers.
What it found
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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
98 citing papers in PubMed, 124 citations in OpenAlex.
- Deciphering resistance mechanisms in cancer: final report of MATCH-R study with a focus on molecular drivers and PDX development.Molecular cancer · 2024Trial
- Efficacy and Safety of Adagrasib plus Cetuximab in Patients with KRASG12C-Mutated Metastatic Colorectal Cancer.Cancer discovery · 2024Trial
- Lineage identity governs oncogene dependence in mouse NSCLC models of KRAS inhibitor resistance.Nature genetics · 2026Article
- Genomic landscape and clinical characteristics of ERBB2/HER2-mutated colorectal cancers.The oncologist · 2026Article
- Oncogenic Kras targeting with MRTX1133 or Daraxonrasib specifically synergize with anti-CTLA4 to promote anti-tumor immunity in pancreatic cancer.Nature communications · 2026Article
- Concurrent genetic and non-genetic resistance mechanisms to KRAS inhibition in colorectal cancer.Cancer cell · 2026Article
- Precision Medicine in Pancreatic Cancer: Targeting KRAS and Beyond.Targeted oncology · 2026Review
- The dynamic evolution of circulating tumor cells during glecirasib treatment predicts survival and resistance in gastrointestinal tumors with KRASHuman cell · 2026Article
- Mevalonate pathway rewiring driven by enhancer remodelling confers resistance to KRAS inhibitors in colorectal cancer.Nature communications · 2026Article
- WEE1 kinase inhibition to overcome acquired resistance to targeted therapies in colorectal cancer.EMBO molecular medicine · 2026Article
- Abrogation of Oncogenic RAS Signaling by a RAS(ON) Inhibitor Doublet Primes Immune-Refractory KRASG12C-Mutant NSCLC for Immune Checkpoint Blockade.Cancer discovery · 2026Article
- 10-Hydroxy-2-decenoic Acid Suppresses Colorectal Cancer Progression by Inhibiting Wnt/β-Catenin Signaling and Promoting Apoptosis.Foods (Basel, Switzerland) · 2026Article
- The Farnesyl Transferase Inhibitor Darlifarnib (KO-2806) Resensitizes Relapsing Tumors to RAS Inhibition.Cancer research · 2026Article
- Characterization of KRASNature communications · 2026Article
- Activity of Direct KRAS(G12C) Inhibitors in Preclinical Models of Pediatric Cancer.Molecular cancer therapeutics · 2026Article
- Recurrent cancer-associated ERBB4 mutations are transforming and confer resistance to targeted therapies.Molecular oncology · 2026Article
- High-throughput screening identifies NT-1 that synergizes with MRTX1133 against acquired resistant KRASNPJ precision oncology · 2026Article
- Acquired High Tumor Mutational Burden and Activity of Immunotherapy after Targeted Therapy in Microsatellite Stable Colorectal Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- mSWI/SNF complex inhibition sensitizes KRAS-mutant lung cancers to targeted therapies via epithelial-mesenchymal subversion.bioRxiv : the preprint server for biology · 2026Article
- The GENEVA platform models tumor mosaicism to reveal variations of responses to KRAS inhibitors and identify improved drug combinations.Nature cancer · 2026Article
38 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
34 authors at 3 institutions in 1 country.
Funding
Abstract
With the combination of KRASG12C and EGFR inhibitors, KRAS is becoming a druggable target in colorectal cancer. However, secondary resistance limits its efficacy. Using cell lines, patient-derived xenografts, and patient samples, we detected a heterogeneous pattern of putative resistance alterations expected primarily to prevent inhibition of ERK signaling by drugs at progression. Serial analysis of patient blood samples on treatment demonstrates that most of these alterations are detected at a low frequency except for KRASG12C amplification, a recurrent resistance mechanism that rises in step with clinical progression. Upon drug withdrawal, resistant cells with KRASG12C amplification undergo oncogene-induced senescence, and progressing patients experience a rapid fall in levels of this alteration in circulating DNA. In this new state, drug resumption is ineffective as mTOR signaling is elevated. However, our work exposes a potential therapeutic vulnerability, whereby therapies that target the senescence response may overcome acquired resistance. SIGNIFICANCE: Clinical resistance to KRASG12C-EGFR inhibition primarily prevents suppression of ERK signaling. Most resistance mechanisms are subclonal, whereas KRASG12C amplification rises over time to drive a higher portion of resistance. This recurrent resistance mechanism leads to oncogene-induced senescence upon drug withdrawal and creates a potential vulnerability to senolytic approaches. This article is highlighted in the In This Issue feature, p. 1.
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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.