ArticleEuropean urology2019
A Whole-genome CRISPR Screen Identifies a Role of MSH2 in Cisplatin-mediated Cell Death in Muscle-invasive Bladder Cancer.
Article in European urology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 1 of them a synthesis that pooled it.
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Who cites it
45 citing papers in PubMed, 1 synthesis or guideline pooled it, 102 citations in OpenAlex.
- Efficacy of Raman spectroscopy in the diagnosis of bladder cancer: A systematic review and meta-analysis.Medicine · 2019Pooled it
- Prediction of pathological response following neoadjuvant chemotherapy in patients with muscle-invasive bladder cancer: the PRE-PREVENCYS trial.BMC cancer · 2021Trial
- Inhibition of TGM2 enhances cisplatin sensitivity in MSH2-deficient bladder cancer.Cell death discovery · 2026Article
- The G protein-coupled receptor GPR89A is a novel potential therapeutic target to overcome cisplatin resistance in NSCLC Calu1 cells.The FEBS journal · 2025Article
- Multiplex gene editing models of del(7q) reveal combinedBlood neoplasia · 2025Article
- WBP1 regulates mitochondrial function and ferroptosis to modulate chemoresistance in colorectal cancer.Molecular medicine (Cambridge, Mass.) · 2025Article
- Mechanisms and therapeutic implications of gene expression regulation by circRNA-protein interactions in cancer.Communications biology · 2025Review
- Key immune cells and their crosstalk in the tumor microenvironment of bladder cancer: insights for innovative therapies.Exploration of targeted anti-tumor therapy · 2025Review
- State of the art CRISPR-based strategies for cancer diagnostics and treatment.Biomarker research · 2024Review
- Article
- NPEPPS Is a Druggable Driver of Platinum Resistance.Cancer research · 2024Article
- Engineering CRISPR/Cas9 therapeutics for cancer precision medicine.Frontiers in genetics · 2024Review
- Lnc-PTCHD4-AS inhibits gastric cancer through MSH2-MSH6 dimerization and ATM-p53-p21 activation.Aging · 2023Article
- Construction and validation of a metabolism-associated gene signature for predicting the prognosis, immune landscape, and drug sensitivity in bladder cancer.BMC medical genomics · 2023Article
- MiR-590-5p promotes cisplatin resistance via targeting hMSH2 in ovarian cancer.Molecular biology reports · 2023Article
- Genome-Wide Screening Identifies Gene AKR1C1 Critical for Resistance to Pirarubicin in Bladder Cancer.Cancers · 2023Article
- hMSH2 coordinated with the expression of E2F1 promotes platinum response in epithelial ovarian cancer.The Journal of international medical research · 2023Article
- Genome-wide CRISPR/Cas9 screening for drug resistance in tumors.Frontiers in pharmacology · 2023Review
- Article
- (Nano)platforms in bladder cancer therapy: Challenges and opportunities.Bioengineering & translational medicine · 2023Review
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundThe response to first-line, platinum-based treatment of muscle-invasive bladder cancer has not improved in 3 decades.
objectiveTo identify genes that influence cisplatin resistance in bladder cancer. DESIGN, SETTING, AND
participantsWe performed a whole-genome CRISPR screen in a bladder cancer cell line to identify genes that mediate resistance to cisplatin. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Targeted validation was performed in two bladder cancer cell lines. The top gene candidate was validated in a publicly available bladder cancer dataset. RESULTS AND LIMITATIONS: From the CRISPR screen, we identified MSH2 as the most significantly enriched gene and mismatch repair as the most significantly enriched pathway that promoted resistance to cisplatin. Bladder cancer cells with knockdown of MSH2 showed a reduction in cisplatin-mediated apoptosis. MSH2 loss did not impact the sensitivity to other chemotherapies, including the cisplatin analog oxaliplatin. Bladder tumors with low MSH2 protein levels, quantified using reverse-phase protein array, showed poorer survival when treated with cisplatin- or carboplatin-based therapy; these results require future validation using immunohistochemistry. Additionally, results are retrospective from patients with primarily high-grade tumors; thus, validation in a controlled clinical trial is needed.
conclusionsWe generated in vitro evidence that bladder cancer cell lines depleted of MSH2 are more resistant to cisplatin. We additionally found an association between low MSH2 in bladder tumors and poorer patient survival when treated with platinum-based chemotherapy. If successfully validated prospectively, MSH2 protein level could assist in the selection of patients for chemotherapy. PATIENT SUMMARY: We report the first evidence that MSH2 protein level may contribute to chemotherapy resistance observed in muscle-invasive bladder cancer. MSH2 has potential as a biomarker predictive of response to platinum-based therapy.
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