ArticleCancer research2026
CRISPR-Cas9 Screening Identifies Resistance Mechanisms to KRAS Inhibition in Pancreatic Cancer.
Article in Cancer research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
6 citing papers in PubMed.
- High-Content CRISPR Screening: Methods and Applications.MedComm · 2026Review
- Overcoming Daraxonrasib Resistance: Allele-Specific Mechanisms Guide Salvage Therapy in Pancreatic Cancer.bioRxiv : the preprint server for biology · 2026Article
- Review
- Inhibition of protein kinase CK2 remodels the tumor immune microenvironment and sensitizes lung cancer to PD-L1 blockade.Experimental hematology & oncology · 2026Article
- CRISPR-Cas9 Therapeutics in Early Clinical Development: Delivery and Molecular Diagnostics.Cells · 2026Review
- TEAD inhibitors re-sensitize drug-resistant NF1 MPNST cells to MEK inhibitors.microPublication biology · 2026Article
Corrections and comments
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Authors and funding
25 authors.
Funding
Abstract
KRAS inhibitors (KRASi) targeting various KRAS mutations have entered clinical trials for pancreatic cancer. Despite promising preliminary clinical responses, most patients relapse due to intrinsic or acquired resistance. Thus, combination treatments are essential to extend the efficacy of KRAS-targeted therapies. To further determine the genetic mechanisms of KRASi resistance, we performed KRASi-anchored CRISPR-Cas9 loss-of-function screens in KRASG12D-, KRASG12C-, KRASG12R-, and KRASQ61H-mutant pancreatic ductal adenocarcinoma (PDAC) cell lines, using six KRASi, to identify genes that modulate sensitivity to KRAS inhibition. Several hits from the screens, including EGFR, CK2, p110α, p110γ, and YAP, were validated by combining targeted inhibitors with KRASi. KRASQ61H-mutant PDAC cell lines were intrinsically less dependent on KRAS for survival than other KRAS mutational subtypes. Furthermore, the EGFR inhibitor erlotinib synergized with the RAS(ON) multiselective inhibitor RMC-7977 in KRASQ61H-mutant PDAC cell lines and in cell lines with highly active EGFR by mitigating ERK rebound activity. KRASi-resistant cell lines featured sustained ERK/MAPK dependence despite decreased ERK activity. Together, these findings enhance the understanding of intrinsic and acquired resistance to KRASi and identify therapeutic vulnerabilities that can potentially be exploited for KRASi combination therapies in patients with pancreatic cancer. SIGNIFICANCE: A comprehensive assessment of genetic modulators of KRAS inhibitor sensitivity identifies combination approaches to increase the efficacy of KRAS inhibitors and demonstrates the limited response of KRASQ61H-mutant cancer cells to KRAS inhibition.
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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 Socratic graph.