ArticleProceedings of the National Academy of Sciences of the United States of America2021
Systems level profiling of chemotherapy-induced stress resolution in cancer cells reveals druggable trade-offs.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
What it found
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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
27 citing papers in PubMed.
- Ceritinib overcomes proteasome inhibitor resistance in multiple myeloma by suppressing the protein folding response.Haematologica · 2026Article
- Therapeutic rescue of pathogenic asparaginyl-tRNA synthetase alleles.Molecular therapy. Nucleic acids · 2026Article
- GCN2 in proteostasis: structural logic, signalling networks and disease.The FEBS journal · 2026Review
- Elevated GCN2 levels in cancer cells confer protection from mitotic stress and faster cell movement.Cellular oncology (Dordrecht, Netherlands) · 2026Article
- A Novel Potent and Selective GCN2 Inhibitor, APL-4098, Has Antileukemic Activity through Dysregulation of Mitochondrial Function.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- Inhibition of the integrated stress response rescues a histidyl-tRNA synthetase variant associated with Charcot-Marie-Tooth disease.NAR molecular medicine · 2026Article
- Mechanisms of mTORC1 and GCN2 amino acid sensing pathways in tumorigenesis and metastatic progression (Review).International journal of molecular medicine · 2026Review
- Drug-tolerant persister cells in cancer: bridging the gaps between bench and bedside.Nature communications · 2025Review
- Carfilzomib resistance in multiple myeloma: A comparative metabolomic analysis.Journal of applied genetics · 2025Article
- Article
- An ISR-independent role of GCN2 prevents excessive ribosome biogenesis and mRNA translation.Life science alliance · 2025Article
- Circadian clock control of interactions between eIF2α kinase CPC-3 and GCN1 with ribosomes regulates rhythmic translation initiation.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Multifaceted role of GCN2 in tumor adaptation and therapeutic targeting.Translational oncology · 2024Review
- Targeting neddylation and sumoylation in chemoresistant triple negative breast cancer.NPJ breast cancer · 2024Article
- Kernel-based joint independence tests for multivariate stationary and non-stationary time series.Royal Society open science · 2023Article
- The GCN2/eIF2αK stress kinase regulates PP1 to ensure mitotic fidelity.EMBO reports · 2023Article
- ERMP1 Facilitates The Malignant Characteristics of Colorectal Cancer Cells through Modulating PI3K/AKT/β-Catenin Pathway and Localization of GRP78.Cell journal · 2023Article
- Activating mutations in EGFR and PI3K promote ATF4 induction for NSCLC cell survival during amino acid deprivation.Heliyon · 2023Article
- Patient-specific and gene-corrected induced pluripotent stem cell-derived endothelial cells elucidate single-cell phenotype of pulmonary veno-occlusive disease.Stem cell reports · 2022Article
- Article
Corrections and comments
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Authors and funding
26 authors.
Funding
Abstract
Cancer cells can survive chemotherapy-induced stress, but how they recover from it is not known. Using a temporal multiomics approach, we delineate the global mechanisms of proteotoxic stress resolution in multiple myeloma cells recovering from proteasome inhibition. Our observations define layered and protracted programs for stress resolution that encompass extensive changes across the transcriptome, proteome, and metabolome. Cellular recovery from proteasome inhibition involved protracted and dynamic changes of glucose and lipid metabolism and suppression of mitochondrial function. We demonstrate that recovering cells are more vulnerable to specific insults than acutely stressed cells and identify the general control nonderepressable 2 (GCN2)-driven cellular response to amino acid scarcity as a key recovery-associated vulnerability. Using a transcriptome analysis pipeline, we further show that GCN2 is also a stress-independent bona fide target in transcriptional signature-defined subsets of solid cancers that share molecular characteristics. Thus, identifying cellular trade-offs tied to the resolution of chemotherapy-induced stress in tumor cells may reveal new therapeutic targets and routes for cancer therapy optimization.
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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 Socratic graph.