ArticleEMBO molecular medicine2020
Acquisition of chromosome instability is a mechanism to evade oncogene addiction.
Article in EMBO molecular medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 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.
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Who cites it
43 citing papers in PubMed, 56 citations in OpenAlex.
- Chromosomal instability in cancer: sources, consequences and new therapeutic opportunities.Signal transduction and targeted therapy · 2026Review
- Chromosomal Instability Drives Glioblastoma Heterogeneity and Therapeutic Opportunities.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Investigating the Consequences of Aneuploidy in Cancer and Normal Tissue.Advances in experimental medicine and biology · 2026Review
- Divergent proteome tolerance against gain and loss of chromosome arms.Molecular cell · 2025Article
- Integrative Proteogenomics and Forward Genetics Reveal a Novel Mitotic Vulnerability in Triple-Negative Breast Cancer.Cancer discovery · 2025Article
- LINC01235 Promotes Clonal Evolution through DNA Replication Licensing-Induced Chromosomal Instability in Breast Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- The Selective WEE1 Inhibitor Azenosertib Shows Synergistic Antitumor Activity with KRASG12C Inhibitors in Preclinical Models.Cancer research communications · 2025Article
- Metabolic plasticity drives specific mechanisms of chemotherapy and targeted therapy resistance in metastatic colorectal cancer.Exploration of targeted anti-tumor therapy · 2025Review
- Loss of EMI1 compromises chromosome stability and is associated with cellular transformation in colonic epithelial cell contexts.British journal of cancer · 2024Article
- Aneuploidy as a driver of human cancer.Nature genetics · 2024Review
- Molecular and Clinical Determinants of Acquired Resistance and Treatment Duration for Targeted Therapies in Colorectal Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- The yin and yang of chromosomal instability in prostate cancer.Nature reviews. Urology · 2024Review
- The two sides of chromosomal instability: drivers and brakes in cancer.Signal transduction and targeted therapy · 2024Review
- Joint global and local interpretation method for CIN status classification in breast cancer.Heliyon · 2024Article
- epiAneufinder identifies copy number alterations from single-cell ATAC-seq data.Nature communications · 2023Article
- Disentangling the roles of aneuploidy, chromosomal instability and tumour heterogeneity in developing resistance to cancer therapies.Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology · 2023Review
- Review
- Mechanisms of chromosomal instability (CIN) tolerance in aggressive tumors: surviving the genomic chaos.Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology · 2023Review
- Review
- Adaptation to spindle assembly checkpoint inhibition through the selection of specific aneuploidies.Genes & development · 2023Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Chromosome instability (CIN) has been associated with therapeutic resistance in many cancers. However, whether tumours become genomically unstable as an evolutionary mechanism to overcome the bottleneck exerted by therapy is not clear. Using a CIN model of Kras-driven breast cancer, we demonstrate that aneuploid tumours acquire genetic modifications that facilitate the development of resistance to targeted therapy faster than euploid tumours. We further show that the few initially chromosomally stable cancers that manage to persist during treatment do so concomitantly with the acquisition of CIN. Whole-genome sequencing analysis revealed that the most predominant genetic alteration in resistant tumours, originated from either euploid or aneuploid primary tumours, was an amplification on chromosome 6 containing the cMet oncogene. We further show that these tumours are dependent on cMet since its pharmacological inhibition leads to reduced growth and increased cell death. Our results highlight that irrespective of the initial CIN levels, cancer genomes are dynamic and the acquisition of a certain level of CIN, either induced or spontaneous, is a mechanism to circumvent oncogene addiction.
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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.