ArticleOncotarget2016
A synthetic-lethality RNAi screen reveals an ERK-mTOR co-targeting pro-apoptotic switch in PIK3CA+ oral cancers.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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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
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 25 citations in OpenAlex.
- Predictive Value of EGFR-PI3K-AKT-mTOR-Pathway Inhibitor Biomarkers for Head and Neck Squamous Cell Carcinoma: A Systematic Review.Molecular diagnosis & therapy · 2021Pooled it
- Inhibition of mTOR Signaling and Clinical Activity of Rapamycin in Head and Neck Cancer in a Window of Opportunity Trial.Clinical cancer research : an official journal of the American Association for Cancer Research · 2019Trial
- The GENEVA platform models tumor mosaicism to reveal variations of responses to KRAS inhibitors and identify improved drug combinations.Nature cancer · 2026Article
- Article
- A 3D generation framework using diffusion model and reinforcement learning to generate multi-target compounds with desired properties.Journal of cheminformatics · 2025Article
- TARGET-SL: precision essential gene prediction using driver prioritisation and synthetic lethality.Briefings in bioinformatics · 2025Article
- A Kinome-Wide Synthetic Lethal CRISPR/Cas9 Screen Reveals That mTOR Inhibition Prevents Adaptive Resistance to CDK4/CDK6 Blockade in HNSCC.Cancer research communications · 2024Article
- Review
- Genome-Wide Super-Enhancer-Based Analysis: Identification of Prognostic Genes in Oral Squamous Cell Carcinoma.International journal of molecular sciences · 2022Article
- Review
- Phenotypic screening using large-scale genomic libraries to identify drug targets for the treatment of cancer.Oncology letters · 2020Review
- PDK1 MediatesClinical cancer research : an official journal of the American Association for Cancer Research · 2019Article
- Synergistic Growth Inhibition by Afatinib and Trametinib in Preclinical Oral Squamous Cell Carcinoma Models.Targeted oncology · 2019Article
- A Platform of Synthetic Lethal Gene Interaction Networks Reveals that the GNAQ Uveal Melanoma Oncogene Controls the Hippo Pathway through FAK.Cancer cell · 2019Article
- Genome-wide prediction of synthetic rescue mediators of resistance to targeted and immunotherapy.Molecular systems biology · 2019Article
- PI3-kinase pathway biomarkers in oral cancer and tumor immune cells.Head & neck · 2019Article
- mTOR co-targeting strategies for head and neck cancer therapy.Cancer metastasis reviews · 2017Review
- Synthetic lethality: emerging targets and opportunities in melanoma.Pigment cell & melanoma research · 2017Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
mTOR inhibition has emerged as a promising strategy for head and neck squamous cell carcinomas (HNSCC) treatment. However, most targeted therapies ultimately develop resistance due to the activation of adaptive survival signaling mechanisms limiting the activity of targeted agents. Thus, co-targeting key adaptive mechanisms may enable more effective cancer cell killing. Here, we performed a synthetic lethality screen using shRNA libraries to identify druggable candidates for combinatorial signal inhibition. We found that the ERK pathway was the most highly represented. Combination of rapamycin with trametinib, a MEK1/2 inhibitor, demonstrated strong synergism in HNSCC-derived cells in vitro and in vivo, including HNSCC cells expressing the HRAS and PIK3CA oncogenes. Interestingly, cleaved caspase-3 was potently induced by the combination therapy in PIK3CA+ cells in vitro and tumor xenografts. Moreover, ectopic expression of PIK3CA mutations into PIK3CA- HNSCC cells sensitized them to the pro-apoptotic activity of the combination therapy. These findings indicate that co-targeting the mTOR/ERK pathways may provide a suitable precision strategy for HNSCC treatment. Moreover, PIK3CA+ HNSCC are particularly prone to undergo apoptosis after mTOR and ERK inhibition, thereby providing a potential biomarker of predictive value for the selection of patients that may benefit from this combination therapy.
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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.