ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2025
A Dual Approach with Organoid and CRISPR Screening Reveals ERCC6 as a Determinant of Cisplatin Resistance in Osteosarcoma.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
17 citing papers in PubMed.
- The Osteosarcoma Tumor Microenvironment: From Cellular Interactions to Advanced Preclinical Models.Cancers · 2026Review
- RNA splicing in health and disease.Molecular biomedicine · 2026Review
- ERCC6 at the Transcription-Replication Interface: Integration of Transcription-Coupled Repair with Replication Stress Responses.International journal of molecular sciences · 2026Review
- HNRNPU K181 Lactylation Drives Cervical Cancer Growth by Upregulating PHGDH and Reprogramming Serine Metabolism.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- LL-37 inhibits osteosarcoma progression by suppressing SQLE-mediated cholesterol synthesis via the PTEN/AKT/mTOR pathway.Journal of bone oncology · 2026Article
- Irisquinone exerts anti-osteosarcoma activity by regulating the PI3K/AKT signaling pathway.Scientific reports · 2026Article
- Nanoparticle-based mechanistic and multifunctional strategies for targeted osteosarcoma therapy.Discover nano · 2026Review
- Reconstruction of T cell infiltration in an osteosarcoma PDX-organoid interactive biobank for personalized immunotherapy.Cell reports. Medicine · 2026Article
- Transcription-Coupled Repair Promotes the Retention of Mutations in Coding Regions During Replication Stress.International journal of molecular sciences · 2026Article
- Organoids glimpse: the nexus for diverse tumor heterogeneity.Frontiers in cell and developmental biology · 2026Review
- Cisplatin resistance in oral squamous cell carcinoma: mechanisms, reversal strategies, and emerging technologies.Frontiers in physiology · 2026Review
- Engineering Osteosarcoma In Vitro: From Traditional Models to Biofabricated Platforms for Precision Medicine.ACS omega · 2025Review
- Molecular mechanisms and genetic predisposition to osteoarthritis and osteosarcoma through Mendelian inheritance patterns.Discover oncology · 2025Article
- Cell and tissue reprogramming: Unlocking a new era in medical drug discovery.Pharmacological reviews · 2025Review
- A Dual Approach with Organoid and CRISPR Screening Reveals ERCC6 as a Determinant of Cisplatin Resistance in Osteosarcoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Studies on the functionality of the TC-NER ERCC6-M1097V protein variant frequently found in Louisiana patients with PCa upon UV damage.Frontiers in oncology · 2025Article
- Intelligent Nanomedicine Systems Utilizing Diverse Nanoparticles for Osteosarcoma Therapy: A Review.International journal of nanomedicine · 2025Review
Corrections and comments
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Authors and funding
12 authors.
Funding
Abstract
Osteosarcoma (OS), the most prevalent primary bone malignancy in adolescents, is typically treated with cisplatin-based chemotherapy. However, the development of cisplatin resistance often leads to relapse or metastasis, significantly impairing therapeutic efficacy. To tackle this issue, patient-derived osteosarcoma organoids (OSOs) is established that accurately reflect the cellular composition and heterogeneity of the original tumors, as validated by single-cell RNA sequencing, bulk RNA sequencing, and histopathology analysis. Cisplatin resistance is successfully induced in these OSOs, creating a clinically relevant model for investigating chemoresistance. Utilizing RNA sequencing in cisplatin-resistance OSOs and CRISPR screening in OS cell line, ERCC6 is identified as a pivotal regulator of cisplatin resistance. Knockdown of ERCC6 markedly enhanced cisplatin sensitivity in vitro and in vivo. Mechanistically, ERCC6 interacts with HNRNPM, influencing the PI3K/AKT signaling pathway and alternative splicing of pre-mRNA for BAX. Notably, the knockdown of ERCC6 and HNRNPM increased expression of full-length BAX and reduced skipping of exon 2, thus promoting apoptosis. This exon skipping in BAX results in a frameshift and introduces a premature stop codon (TGA) within the BH3 domain. These findings underscore the utility of OSOs in elucidating resistance mechanisms and highlight ERCC6 and HNRNPM as potential therapeutic targets.
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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 Socratic graph.