ArticleCell reports. Medicine2020
Overcoming Adaptive Resistance to KRAS and MEK Inhibitors by Co-targeting mTORC1/2 Complexes in Pancreatic Cancer.
Article in Cell reports. Medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers, 1 of them a synthesis that pooled it.
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
82 citing papers in PubMed, 1 synthesis or guideline pooled it, 106 citations in OpenAlex.
- KRAS G12C inhibitors in KRASFrontiers in immunology · 2026Pooled it
- Selumetinib in adults with NF1 and inoperable plexiform neurofibroma: a phase 2 trial.Nature medicine · 2025Trial
- Review
- MicroRNA-15a/16 regulate protein metabolism and are associated with clinical outcomes in pancreatic ductal adenocarcinoma.Physiological reports · 2026Article
- The anticancer effects of PCAIs in pancreatic cancer cells involve MAPK and PI3K/AKT pathways hyperactivation.Oncotarget · 2026Article
- Modulation of Oncogenic KRAS Signaling by Branched Actin-driven Cell Membrane Protrusions.Research square · 2026Article
- Overcoming Adaptive Resistance to KRASG12D Blockade in Pancreatic Cancer through Vertical Pathway Inhibition.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- Acquired resistance of cancer therapies: Mechanisms and perspectives.Chinese medical journal · 2026Review
- Characterization of KRASNature communications · 2026Article
- Modulation of Oncogenic KRAS Signaling by Branched Actin-driven Cell Membrane Protrusions.bioRxiv : the preprint server for biology · 2026Article
- ZBTB11 depletion targets metabolic vulnerabilities in KRAS inhibitor-resistant PDAC.Nature chemical biology · 2026Article
- Phase II Trial of Vemurafenib and Sorafenib Combination in AdvancedJournal of immunotherapy and precision oncology · 2026Article
- Bracing for the storm: emerging resistance mechanisms to KRAS inhibitors in pancreatic cancer and strategies to overcome them.Cancer drug resistance (Alhambra, Calif.) · 2026Review
- Harnessing transcriptomics for discovery of natural products to overcome acquired cancer resistance.Archives of pharmacal research · 2026Review
- Targeting KRAS mutations: orchestrating cancer evolution and therapeutic challenges.Signal transduction and targeted therapy · 2025Review
- RAS Pathway Inhibitors Combined with Targeted Agents Are Active in Patient-Derived Spheroids with Oncogenic KRAS Variants from Multiple Cancer Types.Cancer research communications · 2025Article
- Driving Precision Medicine in Pancreatic Cancer With Molecular Genetics.Seminars in radiation oncology · 2025Review
- DUSP6 is upregulated in metastasis and influences migration and metabolism in pancreatic cancer cells.Scientific reports · 2025Article
- Review
- Selumetinib in Adult Neurofibromatosis 1 with Plexiform Neurofibroma.Pharmaceuticals (Basel, Switzerland) · 2025Article
22 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Activating KRAS mutations are found in over 90% of pancreatic ductal adenocarcinomas (PDACs), yet KRAS has remained a difficult target to inhibit pharmacologically. Here, we demonstrate, using several human and mouse models of PDACs, rapid acquisition of tumor resistance in response to targeting KRAS or MEK, associated with integrin-linked kinase (ILK)-mediated increased phosphorylation of the mTORC2 component Rictor, and AKT. Although inhibition of mTORC1/2 results in a compensatory increase in ERK phosphorylation, combinatorial treatment of PDAC cells with either KRAS (G12C) or MEK inhibitors, together with mTORC1/2 inhibitors, results in synergistic cytotoxicity and cell death reflected by inhibition of pERK and pRictor/pAKT and of downstream regulators of protein synthesis and cell survival. Relative to single agents alone, this combination leads to durable inhibition of tumor growth and metastatic progression
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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.