ArticleEBioMedicine2020
Molecular correlates of sensitivity to PARP inhibition beyond homologous recombination deficiency in pre-clinical models of colorectal cancer point to wild-type TP53 activity.
Article in EBioMedicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 39 citations in OpenAlex.
- Trial
- Sensitizing Colorectal Cancer to PARP Inhibitors: Biomarkers, Mechanisms, and Combination Strategies.International journal of molecular sciences · 2026Review
- Exceptional treatment responses and molecular markers among 103 colorectal cancer cell lines.Molecular biomedicine · 2026Article
- Patient-derived organoids from metastatic colorectal cancer mirror tumor heterogeneity and predict patient survival and drug sensitivity.Cell reports. Medicine · 2026Article
- A novel ex vivo platform for functional evaluation of treatment responses in metastatic ovarian cancer.NPJ precision oncology · 2026Article
- Long-term survival in a patient with BRCA2-mutated pleomorphic anaplastic pancreatic carcinoma treated with Olaparib maintenance therapy.Clinical journal of gastroenterology · 2026Article
- Olaparib for patients with tumors harboring alterations in homologous recombination repair genes: Results from the drug rediscovery protocol.International journal of cancer · 2026Article
- PARP inhibitors across different malignancies: clinical applications, resistance mechanisms, and strategies to enhance efficacy through combination therapies.Frontiers in cell and developmental biology · 2026Review
- MicroRNA-873 Suppresses Viability and Invasion of Colorectal Cancer Through KRAS/MAPK Signaling and Sensitizes Tumor Spheroids to 5-Fluorouracil in a 3D Microwell Model.IEEE open journal of engineering in medicine and biology · 2026Article
- Establishment and characterization of a new immortalized human oral keratinocyte (HOK) cell line harboring various TP53 mutations.Oral oncology · 2026Article
- Unmatched Cell Line Collections Are Not Optimal for Identification of PARP Inhibitor Response and Drug Synergies.Journal of cellular and molecular medicine · 2025Article
- PARP Inhibition in Colorectal Cancer-A Comparison of Potential Predictive Biomarkers for Therapy.Pharmaceuticals (Basel, Switzerland) · 2025Article
- iNOS-Produced Nitric Oxide from Cancer Cells as an Intermediate of Stemness Regulation by PARP-1 in Colorectal Cancer.Biomolecules · 2025Article
- PARP Inhibitors in Colorectal Malignancies: A 2023 Update.Reviews on recent clinical trials · 2024Review
- Unravelling homologous recombination repair deficiency and therapeutic opportunities in soft tissue and bone sarcoma.EMBO molecular medicine · 2023Article
- BRCA Mutations-The Achilles Heel of Breast, Ovarian and Other Epithelial Cancers.International journal of molecular sciences · 2023Review
- PARP-1 Expression Influences Cancer Stem Cell Phenotype in Colorectal Cancer Depending on p53.International journal of molecular sciences · 2023Article
- Nuclear PTEN's Functions in Suppressing Tumorigenesis: Implications for Rare Cancers.Biomolecules · 2023Review
- The synthetic lethality of targeting cell cycle checkpoints and PARPs in cancer treatment.Journal of hematology & oncology · 2022Review
- Exposure to escalating olaparib does not induce acquired resistance to PARPi and to other chemotherapeutic compounds in ovarian cancer cell lines.International journal of oncology · 2022Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundPARP inhibitors are active in various tumour types beyond BRCA-mutant cancers, but their activity and molecular correlates in colorectal cancer (CRC) are not well studied.
methodsMutations and genome-wide mutational patterns associated with homologous recombination deficiency (HRD) were investigated in 255 primary CRCs with whole-exome sequencing and/or DNA copy number data. Efficacy of five PARP inhibitors and their molecular correlates were evaluated in 93 CRC cell lines partly annotated with mutational-, DNA copy number-, and/or gene expression profiles. Post-treatment gene expression profiling and specific protein expression analyses were performed in two pairs of PARP inhibitor sensitive and resistant cell lines.
findingsA subset of microsatellite stable (MSS) CRCs had truncating mutations in homologous recombination-related genes, but these were not associated with genomic signatures of HRD. Eight CRC cell lines (9%) were sensitive to PARP inhibition, but sensitivity was not predicted by HRD-related genomic and transcriptomic signatures. In contrast, drug sensitivity in MSS cell lines was strongly associated with TP53 wild-type status (odds ratio 15.7, p = 0.023) and TP53-related expression signatures. Increased downstream TP53 activity was among the primary response mechanisms, and TP53 inhibition antagonized the effect of PARP inhibitors. Wild-type TP53-mediated suppression of RAD51 was identified as a possible mechanism of action for sensitivity to PARP inhibition.
interpretationPARP inhibitors are active in a subset of CRC cell lines and preserved TP53 function may increase the likelihood of response.
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