ArticlePloS one2018
A CRISPR screen identifies MAPK7 as a target for combination with MEK inhibition in KRAS mutant NSCLC.
Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 24 citations in OpenAlex.
- CRISPR-Cas9 in Cancer Therapy: Overcoming Delivery Barriers and Off-Target Effects for Clinical Translation.Health science reports · 2026Article
- AXL is a novel ERK5/KLF4 target in MEK inhibitor-treated melanoma.Neoplasia (New York, N.Y.) · 2026Article
- MEK5/ERK5 inhibition sensitizes NRAS-mutant melanoma to MAPK-targeted therapy by preventing Cyclin D/CDK4-mediated G1/S progression.Cell death & disease · 2025Article
- Harnessing CRISPR/Cas9 to overcome targeted therapy resistance in non‑small cell lung cancer: Advances and challenges (Review).Oncology reports · 2025Review
- A CRISPR/Cas9 screen reveals proteins at the endosome-Golgi interface that modulate cellular anti-sense oligonucleotide activity.Nature communications · 2025Article
- Is the MAPK ERK5 the nexus from FAO to NK cell-mediated metastasis immune surveillance?Frontiers in immunology · 2025Review
- Personalizing Therapy Outcomes through Mitogen-Activated Protein Kinase Pathway Inhibition in Non-Small Cell Lung Cancer.Biomedicines · 2024Review
- CRISPRingCancers · 2024Review
- Synthetic Vulnerabilities in the KRAS Pathway.Cancers · 2022Review
- Evolution of Molecular Targeted Cancer Therapy: Mechanisms of Drug Resistance and Novel Opportunities Identified by CRISPR-Cas9 Screening.Frontiers in oncology · 2022Review
- CRISPR and KRAS: a match yet to be made.Journal of biomedical science · 2021Review
- Emerging strategies to target RAS signaling in human cancer therapy.Journal of hematology & oncology · 2021Review
- The MEK5/ERK5 Pathway in Health and Disease.International journal of molecular sciences · 2021Review
- CRISPR-Cas deployment in non-small cell lung cancer for target screening, validations, and discoveries.Cancer gene therapy · 2021Review
- PPP6C negatively regulates oncogenic ERK signaling through dephosphorylation of MEK.Cell reports · 2021Article
- Molecular Mechanisms of Epithelial to Mesenchymal Transition Regulated by ERK5 Signaling.Biomolecules · 2021Review
- Playing the Whack-A-Mole Game: ERK5 Activation Emerges Among the Resistance Mechanisms to RAF-MEK1/2-ERK1/2- Targeted Therapy.Frontiers in cell and developmental biology · 2021Review
- Synthetic Lethal Interaction of SHOC2 Depletion with MEK Inhibition in RAS-Driven Cancers.Cell reports · 2019Article
- Disruptive Technology: CRISPR/Cas-Based Tools and Approaches.Molecular diagnosis & therapy · 2019Review
Corrections and comments
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Authors and funding
11 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mutant KRAS represents one of the most frequently observed oncogenes in NSCLC, yet no therapies are approved for tumors that express activated KRAS variants. While there is strong rationale for the use of MEK inhibitors to treat tumors with activated RAS/MAPK signaling, these have proven ineffective clinically. We therefore implemented a CRISPR screening approach to identify novel agents to sensitize KRAS mutant NSCLC cells to MEK inhibitor treatment. This approach identified multiple components of the canonical RAS/MAPK pathway consistent with previous studies. In addition, we identified MAPK7 as a novel, strong hit and validated this finding using multiple orthogonal approaches including knockdown and pharmacological inhibition. We show that MAPK7 inhibition attenuates the re-activation of MAPK signaling occurring following long-term MEK inhibition, thereby illustrating that MAPK7 mediates pathway reactivation in the face of MEK inhibition. Finally, genetic knockdown of MAPK7 combined with the MEK inhibitor cobimetinib in a mutant KRAS NSCLC xenograft model to mediate improved tumor growth inhibition. These data highlight that MAPK7 represents a promising target for combination treatment with MEK inhibition in KRAS mutant NSCLC.
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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.