ArticleeLife2024
Cancers adapt to their mutational load by buffering protein misfolding stress.
Article in eLife, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07715903 (Phase I Study Evaluating Hepatic Artery Infusion of Carfilzomib in Participants With Liver Metastatic Disease Previously Treated With Hepatic Artery Infusion Pump Therapy), which is not on this map. Cited by 8 papers.
What it found
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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.
Phase I Study Evaluating Hepatic Artery Infusion of Carfilzomib in Participants With Liver Metastatic Disease Previously Treated With Hepatic Artery Infusion Pump Therapy
Who cites it
8 citing papers in PubMed.
- Synergistic antiviral effects of structure-guided peptides and a mutagenic base analog on SARS-CoV-2 replication.Antimicrobial agents and chemotherapy · 2026Article
- Impact of proteostasis workload on sensitivity to proteasome inhibitors in multiple myeloma.Clinical and experimental medicine · 2025Review
- Increased expression of DNAJC7 promotes the progression of hepatocellular carcinoma by influencing the cell cycle and immune microenvironment.Journal of cancer research and clinical oncology · 2025Article
- Aggregating amyloid resources: A comprehensive review of databases on amyloid-like aggregation.Computational and structural biotechnology journal · 2024Review
- The Hsp90 Molecular Chaperone as a Global Modifier of the Genotype-Phenotype-Fitness Map: An Evolutionary Perspective.Journal of molecular biology · 2024Review
- Mutational robustness and the role of buffer genes in evolvability.The EMBO journal · 2024Review
- HRS mediates tumor immune evasion by regulating proteostasis-associated interferon pathway activation.Cell reports · 2023Article
- Pervasive aggregation and depletion of host and viral proteins in response to cysteine-reactive electrophilic compounds.bioRxiv : the preprint server for biology · 2023Article
Corrections and comments
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Authors and funding
4 authors.
Funding
Abstract
In asexual populations that don't undergo recombination, such as cancer, deleterious mutations are expected to accrue readily due to genome-wide linkage between mutations. Despite this mutational load of often thousands of deleterious mutations, many tumors thrive. How tumors survive the damaging consequences of this mutational load is not well understood. Here, we investigate the functional consequences of mutational load in 10,295 human tumors by quantifying their phenotypic response through changes in gene expression. Using a generalized linear mixed model (GLMM), we find that high mutational load tumors up-regulate proteostasis machinery related to the mitigation and prevention of protein misfolding. We replicate these expression responses in cancer cell lines and show that the viability in high mutational load cancer cells is strongly dependent on complexes that degrade and refold proteins. This indicates that the upregulation of proteostasis machinery is causally important for high mutational burden tumors and uncovers new therapeutic vulnerabilities.
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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.