ArticleCell reports2017
A Landscape of Therapeutic Cooperativity in KRAS Mutant Cancers Reveals Principles for Controlling Tumor Evolution.
Article in Cell reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
What it found
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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
59 citing papers in PubMed, 86 citations in OpenAlex.
- Tissue and CD4 T cell subset dependence on the amino acid transporter SLC38A1.Cell metabolism · 2026Article
- Article
- KRAS mutations promote PD-L1-mediated immune escape by ETV4 in lung adenocarcinoma.Translational oncology · 2025Article
- KSR1 Mediates Small Cell Lung Carcinoma Tumor Initiation and Cisplatin Resistance.Molecular cancer research : MCR · 2025Article
- Hydroxychloroquine prevents resistance and potentiates the antitumor effect of SHP2 inhibition in NF1-associated malignant peripheral nerve sheath tumors.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Genetics and biology of pancreatic ductal adenocarcinoma.Genes & development · 2025Review
- Mediator kinase inhibition impedes transcriptional plasticity and prevents resistance to ERK/MAPK-targeted therapy in KRAS-mutant cancers.NPJ precision oncology · 2024Article
- Article
- Frequency-dependent ecological interactions increase the prevalence, and shape the distribution, of pre-existing drug resistance.bioRxiv : the preprint server for biology · 2024Article
- SOS2 modulates the threshold of EGFR signaling to regulate osimertinib efficacy and resistance in lung adenocarcinoma.Molecular oncology · 2024Article
- CRISPRingCancers · 2024Review
- Article
- SOS1 and KSR1 modulate MEK inhibitor responsiveness to target resistant cell populations based on PI3K and KRAS mutation status.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Mediator Kinase Inhibition Impedes Transcriptional Plasticity and Prevents Resistance to ERK/MAPK-Targeted Therapy in KRAS-Mutant Cancers.Research square · 2023Article
- CBF-Beta Mitigates PI3K-Alpha-Specific Inhibitor Killing through PIM1 in PIK3CA-Mutant Gastric Cancer.Molecular cancer research : MCR · 2023Article
- SOS2 regulates the threshold of mutantbioRxiv : the preprint server for biology · 2023Article
- Multi-faceted CRISPR/Cas technological innovation aspects in the framework of 3P medicine.The EPMA journal · 2023Review
- BCL2L11 Induction Mediates Sensitivity to Src and MEK1/2 Inhibition in Thyroid Cancer.Cancers · 2023Article
- Applications of CRISPR-Cas9 for advancing precision medicine in oncology: from target discovery to disease modeling.Frontiers in genetics · 2023Review
- Early Combined SHP2 Targeting Reverses the Therapeutic Resistance of Vemurafenib in Thyroid Cancer.Journal of Cancer · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
22 authors at 2 institutions in 1 country.
Funding
Abstract
Combinatorial inhibition of effector and feedback pathways is a promising treatment strategy for KRAS mutant cancers. However, the particular pathways that should be targeted to optimize therapeutic responses are unclear. Using CRISPR/Cas9, we systematically mapped the pathways whose inhibition cooperates with drugs targeting the KRAS effectors MEK, ERK, and PI3K. By performing 70 screens in models of KRAS mutant colorectal, lung, ovarian, and pancreas cancers, we uncovered universal and tissue-specific sensitizing combinations involving inhibitors of cell cycle, metabolism, growth signaling, chromatin regulation, and transcription. Furthermore, these screens revealed secondary genetic modifiers of sensitivity, yielding a SRC inhibitor-based combination therapy for KRAS/PIK3CA double-mutant colorectal cancers (CRCs) with clinical potential. Surprisingly, acquired resistance to combinations of growth signaling pathway inhibitors develops rapidly following treatment, but by targeting signaling feedback or apoptotic priming, it is possible to construct three-drug combinations that greatly delay its emergence.
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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.