ArticleClinical cancer research : an official journal of the American Association for Cancer Research2021
Synthetic Lethal Screens Reveal Cotargeting FAK and MEK as a Multimodal Precision Therapy for
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 54 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
54 citing papers in PubMed, 1 synthesis or guideline pooled it, 74 citations in OpenAlex.
- The Hippo signalling pathway and its impact on eye diseases.Journal of cellular and molecular medicine · 2024Pooled it
- Hypoxia-activated PROTAC for dual inhibition of FAK and EGFR enables synergistic mechano-chemical cancer therapy.Neoplasia (New York, N.Y.) · 2026Article
- A Phase II Trial of Defactinib Combined with Avutometinib in Patients with Metastatic Uveal Melanoma.Cancers · 2026Article
- Demographic trends and geographic disparities in malignant neoplasm of eye and adnexa-related mortality in the United States, 1999-2023.Eye (London, England) · 2026Article
- Genome-wide CRISPR Screening Reveals a PKA-Driven Resistance Mechanism to Metformin for Oral Cancer Prevention That Can Be Exploited by Combination with NSAIDs.Cancer prevention research (Philadelphia, Pa.) · 2026Article
- Inhibition of focal adhesion kinase impairs tumor formation and preserves hearing in a murine model of NF2-related schwannomatosis.Science advances · 2026Article
- Article
- Structure-based identification of novel FAK1 inhibitors using pharmacophore modeling, molecular dynamics, and MM/PBSA calculations.Scientific reports · 2025Article
- Inhibition of anti-apoptotic BCL2 overcomes adaptive resistance to co-targeting of the protein kinase FAK and MEK in GNAQ-driven uveal melanoma.The Journal of biological chemistry · 2025Article
- Defactinib with avutometinib in patients with solid tumors: the phase 1 FRAME trial.Nature medicine · 2025Article
- Genome-Wide CRISPR Screening Reveals That mTOR Inhibition Initiates Ferritinophagy and Ferroptosis in Head and Neck Cancer.Cancer research · 2025Article
- Chromosomal 3p loss and 8q gain drive vasculogenic mimicry via HIF-2α and VE-cadherin activation in uveal melanoma.Cell death and differentiation · 2025Article
- State-of-the-art in Metastatic Uveal Melanoma Treatment: A 2025 Update : How to treat Metastatic Uveal Melanoma in 2025.Current oncology reports · 2025Review
- The guanine nucleotide exchange factor Ric-8A regulates the sensitivity of constitutively active Gαq to the inhibitor YM-254890.The Journal of biological chemistry · 2025Article
- Drug Combinations Targeting FAK and MEK Overcomes Tumor Heterogeneity in Glioblastoma.Pharmaceutics · 2025Article
- Targeting YAP/TAZ-TEAD signaling as a therapeutic approach in head and neck squamous cell carcinoma.Cancer letters · 2025Article
- Combined inhibition of focal adhesion kinase and RAF/MEK elicits synergistic inhibition of melanoma growth and reduces metastases.Cell reports. Medicine · 2025Article
- LHPP Attenuates Lipid Dysfunction of Uveal Melanoma by Relieving the Histidine Phosphorylation of ACO2.Research (Washington, D.C.) · 2025Article
- Nuclear Focal Adhesion Kinase Protects against Cisplatin Stress in Ovarian Carcinoma.Cancer research communications · 2024Article
- Diffuse Gastric Cancer: A Comprehensive Review of Molecular Features and Emerging Therapeutics.Targeted oncology · 2024Review
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
18 authors at 5 institutions in 1 country.
Funding
Abstract
purposeUveal melanoma is the most common eye cancer in adults. Approximately 50% of patients with uveal melanoma develop metastatic uveal melanoma (mUM) in the liver, even after successful treatment of the primary lesions. mUM is refractory to current chemo- and immune-therapies, and most mUM patients die within a year. Uveal melanoma is characterized by gain-of-function mutations in EXPERIMENTAL
designWe performed a kinome-wide CRISPR-Cas9 sgRNA screen to identify synthetic lethal gene interactions that can be exploited therapeutically. Candidate adaptive resistance mechanisms were investigated by cotargeting strategies in uveal melanoma and mUM
resultssgRNAs targeting the PKC and MEK-ERK signaling pathways were significantly depleted after FAK inhibition, with ERK activation representing a predominant resistance mechanism. Pharmacologic inhibition of MEK and FAK showed remarkable synergistic growth-inhibitory effects in uveal melanoma cells and exerted cytotoxic effects, leading to tumor collapse in uveal melanoma xenograft and liver mUM models
conclusionsCoupling the unique genetic landscape of uveal melanoma with the power of unbiased genetic screens, our studies reveal that FAK and MEK-ERK cotargeting may provide a new network-based precision therapeutic strategy for mUM treatment.
Indexed as
Identifiers
What OpenQuestion holds
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.