ArticleThe EMBO journal2020
Reprogrammed mRNA translation drives resistance to therapeutic targeting of ribosome biogenesis.
Article in The EMBO journal, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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
20 citing papers in PubMed, 31 citations in OpenAlex.
- RIOK2 Promotes Clear Cell Renal Cell Carcinoma Progression Through Cell Cycle Regulation.Cancer medicine · 2026Article
- Ribosome biogenesis as a potential therapeutic target in KRAS mutant colorectal cancer.Nature communications · 2025Article
- Targeting ribosomes reprograms the tumour microenvironment and augments cancer immunotherapy.British journal of cancer · 2025Article
- Review
- Identification of programmed cell death-related genes and construction of a prognostic model in oral squamous cell carcinoma using single-cell and transcriptome analysis.Discover oncology · 2025Article
- Ribosome-directed cancer therapies: the tip of the iceberg?Trends in pharmacological sciences · 2025Review
- Molecular Mechanisms of Drug Resistance inPathogens (Basel, Switzerland) · 2024Review
- Next generation sequencing technologies to address aberrant mRNA translation in cancer.NAR cancer · 2024Review
- ATP1A3 regulates protein synthesis for mitochondrial stability under heat stress.Disease models & mechanisms · 2024Article
- Targeting the ribosome to treat multiple myeloma.Molecular therapy. Oncology · 2024Article
- Reducing the metabolic burden of rRNA synthesis promotes healthy longevity in Caenorhabditis elegans.Nature communications · 2024Article
- cAMP-PKA/EPAC signaling and cancer: the interplay in tumor microenvironment.Journal of hematology & oncology · 2024Review
- Transcriptome profile of halofuginone resistant and sensitive strains ofFrontiers in microbiology · 2023Article
- Prostate cancer resistance leads to a global deregulation of translation factors and unconventional translation.NAR cancer · 2022Article
- Anota2seq Analysis for Transcriptome-Wide Studies of mRNA Translation.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Prioritizing key synergistic circulating microRNAs for the early diagnosis of biliary tract cancer.Frontiers in oncology · 2022Article
- G-quadruplex DNA: a novel target for drug design.Cellular and molecular life sciences : CMLS · 2021Review
- Ribosomal proteins and human diseases: molecular mechanisms and targeted therapy.Signal transduction and targeted therapy · 2021Review
- Review
- Reprogrammed mRNA translation drives resistance to therapeutic targeting of ribosome biogenesis.The EMBO journal · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 4 institutions in 3 countries.
Funding
Abstract
Elevated ribosome biogenesis in oncogene-driven cancers is commonly targeted by DNA-damaging cytotoxic drugs. Our previous first-in-human trial of CX-5461, a novel, less genotoxic agent that specifically inhibits ribosome biogenesis via suppression of RNA polymerase I (Pol I) transcription, revealed single-agent efficacy in refractory blood cancers. Despite this clinical response, patients were not cured. In parallel, we demonstrated a marked improvement in the in vivo efficacy of CX-5461 in combination with PI3K/AKT/mTORC1 pathway inhibitors. Here, we reveal the molecular basis for this improved efficacy observed in vivo, which is associated with specific suppression of translation of mRNAs encoding regulators of cellular metabolism. Importantly, acquired resistance to this cotreatment is driven by translational rewiring that results in dysregulated cellular metabolism and induction of a cAMP-dependent pathway critical for the survival of blood cancers including lymphoma and acute myeloid leukemia. Our studies thus identify key molecular mechanisms underpinning the response of blood cancers to selective inhibition of ribosome biogenesis and define metabolic vulnerabilities that will facilitate the rational design of more effective regimens for Pol I-directed therapies.
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.