ArticleBritish journal of cancer2022
CHK2 activation contributes to the development of oxaliplatin resistance in colorectal cancer.
Article in British journal of cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 33 citations in OpenAlex.
- Epacadostat and Olaparib Synergistically Inhibit the Growth of BRCA-Proficient Triple-Negative Breast Cancer by Suppressing the Expression of BRCA1 and RAD51.Molecules (Basel, Switzerland) · 2026Article
- Elevated NDRG1 Expression Drives Oxaliplatin Chemoresistance in Bladder Cancer Cells by Promoting Homologous Recombination Repair and Inhibiting GCell biochemistry and biophysics · 2026Article
- The liver talks back: NPY orchestrates attraction of cancer cells and CHK2-dependent clonogenicity in the metastatic niche.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- ACSL6 modulates docosahexaenoic acid-induced cytotoxicity to potentiate chemotherapy response in colorectal and breast cancer.Oncogenesis · 2025Article
- Discriminating activating, deactivating and resistance variants in protein kinases.Genome medicine · 2025Article
- Repurposing Doxycycline to Overcome High-Glucose-Induced Mitochondrial Biogenesis-Mediated Chemoresistance in Colorectal Cancer Cells.Journal of cellular and molecular medicine · 2025Article
- A FANCD2 gene mutation case analysis providing potential insights into the molecular mechanisms of gastric adenocarcinoma: A case report.Oncology letters · 2025Article
- Tetraarsenic Hexoxide Enhanced the Anticancer Effects ofInternational journal of molecular sciences · 2025Article
- DNA repair and the contribution to chemotherapy resistance.Genome medicine · 2025Review
- HDGF Knockout Suppresses Colorectal Cancer Progression and Drug Resistance by Modulating the DNA Damage Response.Biomolecules · 2025Article
- Guarding against digestive-system cancers: Unveiling the role of Chk2 as a potential therapeutic target.Genes & diseases · 2025Review
- RCC1 knockdown sensitizes drug-resistant colorectal cancer to 5-fluorouracil or doxorubicin by impairing DNA repair.Cancer drug resistance (Alhambra, Calif.) · 2025Article
- A missense variant effect map for the human tumor-suppressor protein CHK2.American journal of human genetics · 2024Article
- The unique Pt(II)-induced nucleolar stress response and its deviation from DNA damage response pathways.The Journal of biological chemistry · 2024Article
- DKK1 as a chemoresistant protein modulates oxaliplatin responses in colorectal cancer.Oncogenesis · 2024Article
- The novel SMYD3 inhibitor EM127 impairs DNA repair response to chemotherapy-induced DNA damage and reverses cancer chemoresistance.Journal of experimental & clinical cancer research : CR · 2024Article
- Resveratrol as sensitizer in colorectal cancer plasticity.Cancer metastasis reviews · 2024Review
- FOXP3-regulated lncRNA NONHSAT136151 promotes colorectal cancer progression by disrupting QKI interaction with target mRNAs.Journal of cellular and molecular medicine · 2024Article
- β-Lapachone Exerts Anticancer Effects by Downregulating p53, Lys-Acetylated Proteins, TrkA, p38 MAPK, SOD1, Caspase-2, CD44 and NPM in Oxaliplatin-Resistant HCT116 Colorectal Cancer Cells.International journal of molecular sciences · 2023Article
- Could Inhibiting the DNA Damage Repair Checkpoint Rescue Immune-Checkpoint-Inhibitor-Resistant Endometrial Cancer?Journal of clinical medicine · 2023Review
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundColorectal cancer (CRC), the most common cancer type, causes high morbidity and mortality. Patients who develop drug resistance to oxaliplatin-based regimens have short overall survival. Thus, identifying molecules involved in the development of oxaliplatin resistance is critical for designing therapeutic strategies.
methodsA proteomic screen was performed to reveal altered protein kinase phosphorylation in oxaliplatin-resistant (OR) CRC tumour spheroids. The function of CHK2 was characterised using several biochemical techniques and evident using in vitro cell and in vivo tumour models.
resultsWe revealed that the level of phospho-CHK2(Thr68) was elevated in OR CRC cells and in ~30% of tumour samples from patients with OR CRC. We demonstrated that oxaliplatin activated several phosphatidylinositol 3-kinase-related kinases (PIKKs) and CHK2 downstream effectors and enhanced CHK2/PARP1 interaction to facilitate DNA repair. A phosphorylation mimicking CHK2 mutant, CHK2T68D, but not a kinase-dead CHK2 mutant, CHK2D347A, promoted DNA repair, the CHK2/PARP1 interaction, and cell growth in the presence of oxaliplatin. Finally, we showed that a CHK2 inhibitor, BML-277, reduced protein poly(ADP-ribosyl)ation (PARylation), FANCD2 monoubiquitination, homologous recombination and OR CRC cell growth in vitro and in vivo.
conclusionOur findings suggest that CHK2 activity is critical for modulating oxaliplatin response and that CHK2 is a potential therapeutic target for OR CRC.
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