ArticleOncotarget2015
High-throughput simultaneous screen and counterscreen identifies homoharringtonine as synthetic lethal with von Hippel-Lindau loss in renal cell carcinoma.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
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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.
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Who cites it
23 citing papers in PubMed, 34 citations in OpenAlex.
- VHL synthetic lethality screens uncover CBF-β as a negative regulator of STING.Nature communications · 2026Article
- Identification of BET inhibitors (BETi) against solitary fibrous tumor (SFT) through high-throughput screening (HTS).Neoplasia (New York, N.Y.) · 2025Article
- Von Hippel-Lindau protein signalling in clear cell renal cell carcinoma.Nature reviews. Urology · 2024Review
- Transcriptional-translational conflict is a barrier to cellular transformation and cancer progression.Cancer cell · 2023Article
- Targeting the translational machinery in gastrointestinal stromal tumors (GIST): a new therapeutic vulnerability.Scientific reports · 2022Article
- A renal cell carcinoma tumorgraft platform to advance precision medicine.Cell reports · 2021Article
- Von Hippel-Lindau tumor suppressor pathways & corresponding therapeutics in kidney cancer.Journal of genetics and genomics = Yi chuan xue bao · 2021Review
- The mProceedings of the National Academy of Sciences of the United States of America · 2020Article
- Homoharringtonine suppresses tumor proliferation and migration by regulating EphB4-mediated β-catenin loss in hepatocellular carcinoma.Cell death & disease · 2020Article
- Article
- TBK1 Is a Synthetic Lethal Target in Cancer withCancer discovery · 2020Article
- HIF-independent synthetic lethality between CDK4/6 inhibition and VHL loss across species.Science signaling · 2019Article
- Next Generation Sequencing in Renal Cell Carcinoma: Towards Precision Medicine.Kidney cancer journal : official journal of the Kidney Cancer Association · 2019Article
- Targeting the Mevalonate Pathway Suppresses VHL-Deficient CC-RCC through an HIF-Dependent Mechanism.Molecular cancer therapeutics · 2018Article
- VHL and Hypoxia Signaling: Beyond HIF in Cancer.Biomedicines · 2018Review
- Patient-derived xenografts as in vivo models for research in urological malignancies.Nature reviews. Urology · 2017Review
- Rho-associated kinase 1 inhibition is synthetically lethal with von Hippel-Lindau deficiency in clear cell renal cell carcinoma.Oncogene · 2017Article
- The Expression of VHL (Von Hippel-Lindau) After Traumatic Spinal Cord Injury and Its Role in Neuronal Apoptosis.Neurochemical research · 2016Article
- Physapubescin selectively induces apoptosis in VHL-null renal cell carcinoma cells through down-regulation of HIF-2α and inhibits tumor growth.Scientific reports · 2016Article
- Article
Corrections and comments
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
Renal cell carcinoma (RCC) accounts for 85% of primary renal neoplasms, and is rarely curable when metastatic. Approximately 70% of RCCs are clear-cell type (ccRCC), and in >80% the von Hippel-Lindau (VHL) gene is mutated or silenced. We developed a novel, high-content, screening strategy for the identification of small molecules that are synthetic lethal with genes mutated in cancer. In this strategy, the screen and counterscreen are conducted simultaneously by differentially labeling mutant and reconstituted isogenic tumor cell line pairs with different fluorochromes and using a highly sensitive high-throughput imaging-based platform. This approach minimizes confounding factors from sequential screening, and more accurately replicates the in vivo cancer setting where cancer cells are adjacent to normal cells. A screen of ~12,800 small molecules identified homoharringtonine (HHT), an FDA-approved drug for treating chronic myeloid leukemia, as a VHL-synthetic lethal agent in ccRCC. HHT induced apoptosis in VHL-mutant, but not VHL-reconstituted, ccRCC cells, and inhibited tumor growth in 30% of VHL-mutant patient-derived ccRCC tumorgraft lines tested. Building on a novel screening strategy and utilizing a validated RCC tumorgraft model recapitulating the genetics and drug responsiveness of human RCC, these studies identify HHT as a potential therapeutic agent for a subset of VHL-deficient ccRCCs.
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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.