ArticleNature medicine2014
In vivo RNAi screening identifies a mechanism of sorafenib resistance in liver cancer.
Article in Nature medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 158 papers.
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Who cites it
158 citing papers in PubMed, 276 citations in OpenAlex.
- Impact of neo-adjuvant Sorafenib treatment on liver transplantation in HCC patients - a prospective, randomized, double-blind, phase III trial.BMC cancer · 2015Trial
- Targeting p38α in cancer: challenges, opportunities, and emerging strategies.Molecular oncology · 2026Review
- Integrated in vivo combinatorial functional genomics and spatial transcriptomics of tumours to decode genotype-to-phenotype relationships.Nature biomedical engineering · 2026Article
- Loss of ELF2 drives topotecan resistance in retinoblastoma revealed by genome-wide CRISPR-Cas9 screening.Cell death & disease · 2025Article
- Discovery of the First Highly Selective 1,4-dihydropyrido[3,4-Journal of medicinal chemistry · 2025Article
- Differential expression pattern of CC chemokine receptor 7 guides precision treatment of hepatocellular carcinoma.Signal transduction and targeted therapy · 2025Article
- IFNγ augments TKI efficacy by alleviating protein unfolding stress to promote GSDME-mediated pyroptosis in hepatocellular carcinoma.Cell death & disease · 2025Article
- In vivo CRISPR screening identifies POU3F3 as a novel regulator of ferroptosis resistance in hepatocellular carcinoma via retinoic acid signaling.Cell communication and signaling : CCS · 2025Article
- A stress-responsive p38 signaling axis in choanoflagellates.RSC chemical biology · 2025Article
- Active repression of cell fate plasticity by PROX1 safeguards hepatocyte identity and prevents liver tumorigenesis.Nature genetics · 2025Article
- First-in-class ultralong-target-residence-time p38α inhibitors as a mitosis-targeted therapy for colorectal cancer.Nature cancer · 2025Article
- Role of immune cell homeostasis in research and treatment response in hepatocellular carcinoma.Clinical and experimental medicine · 2025Article
- Article
- Emerging trends and knowledge networks in pan-cancer sorafenib resistance: a 20-year bibliometric investigation.Frontiers in pharmacology · 2025Article
- Article
- Intracellular magnetic hyperthermia reverses sorafenib resistance in hepatocellular carcinoma through its action on signaling pathways.iScience · 2024Article
- Advances in Making Cancer Mouse Models More Accessible and Informative through Non-Germline Genetic Engineering.Cold Spring Harbor perspectives in medicine · 2024Review
- Article
- Molecular diagnostics of hepatobiliary and pancreatic neoplasias.Virchows Archiv : an international journal of pathology · 2024Review
- HDAC-driven mechanisms in anticancer resistance: epigenetics and beyond.Cancer drug resistance (Alhambra, Calif.) · 2024Review
98 more citing papers are in PubMed but not listed here.
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Authors and funding
21 authors at 9 institutions in 3 countries.
Funding
Abstract
In solid tumors, resistance to therapy inevitably develops upon treatment with cytotoxic drugs or molecularly targeted therapies. Here, we describe a system that enables pooled shRNA screening directly in mouse hepatocellular carcinomas (HCC) in vivo to identify genes likely to be involved in therapy resistance. Using a focused shRNA library targeting genes located within focal genomic amplifications of human HCC, we screened for genes whose inhibition increased the therapeutic efficacy of the multikinase inhibitor sorafenib. Both shRNA-mediated and pharmacological silencing of Mapk14 (p38α) were found to sensitize mouse HCC to sorafenib therapy and prolong survival by abrogating Mapk14-dependent activation of Mek-Erk and Atf2 signaling. Elevated Mapk14-Atf2 signaling predicted poor response to sorafenib therapy in human HCC, and sorafenib resistance of p-Mapk14-expressing HCC cells could be reverted by silencing Mapk14. Our results suggest that a combination of sorafenib and Mapk14 blockade is a promising approach to overcoming therapy resistance of human HCC.
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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.