ArticleInternational journal of molecular sciences2021
Targeting of Deregulated Wnt/β-Catenin Signaling by PRI-724 and LGK974 Inhibitors in Germ Cell Tumor Cell Lines.
Article in International journal of molecular sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 23 citations in OpenAlex.
- Targeting molecular and genetic pathways driving tumorigenesis for precision therapy in colorectal cancer.Cancer biology & therapy · 2026Review
- Comparative Molecular and Genetic Landscape of Gonadal Germ Cell Tumors: Insights from Testicular and Ovarian Neoplasms.Cancers · 2026Review
- CDK4 inhibition by luteolin enhances lenvatinib sensitivity in HCC via Wnt/β-catenin modulation.Cancer cell international · 2026Article
- Chemoresistance: The hidden barrier in cancer treatment.Cancer pathogenesis and therapy · 2026Review
- Advancements in single-cell sequencing for cervical cancer research.Molecular and cellular biochemistry · 2026Review
- Epithelial‑mesenchymal plasticity and cisplatin resistance in germ cell tumors: Mechanisms and emerging therapeutic strategies (Review).International journal of oncology · 2025Review
- Article
- Cancer stem cells: landscape, challenges and emerging therapeutic innovations.Signal transduction and targeted therapy · 2025Review
- Signaling pathway dysregulation in breast cancer.Oncotarget · 2025Review
- Review
- Article
- Redefining Therapeutic Approaches in Colorectal Cancer: Targeting Molecular Pathways and Overcoming Resistance.International journal of molecular sciences · 2024Review
- Wnt signaling: Essential roles in osteoblast differentiation, bone metabolism and therapeutic implications for bone and skeletal disorders.Genes & diseases · 2023Review
- Combinations of PRI-724 Wnt/β-Catenin Pathway Inhibitor with Vismodegib, Erlotinib, or HS-173 Synergistically Inhibit Head and Neck Squamous Cancer Cells.International journal of molecular sciences · 2023Article
- Breaking the Mold: Epigenetics and Genomics Approaches Addressing Novel Treatments and Chemoresponse in TGCT Patients.International journal of molecular sciences · 2023Review
- Prognostic role of plasma vitamin D and its association with disease characteristics in germ cell tumours.Frontiers in oncology · 2023Article
- Effect of the PARP inhibitor veliparib on germ cell tumor cell lines.Oncology letters · 2022Article
- Current Approaches in Hepatoblastoma-New Biological Insights to Inform Therapy.Current oncology reports · 2022Review
- Overcoming Chemotherapy Resistance in Germ Cell Tumors.Biomedicines · 2022Review
- WNT Signaling as a Therapeutic Target for Glioblastoma.International journal of molecular sciences · 2021Review
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 2 countries.
Funding
Abstract
The majority of patients with testicular germ cell tumors (GCTs) can be cured with cisplatin-based chemotherapy. However, for a subset of patients present with cisplatin-refractory disease, which confers a poor prognosis, the treatment options are limited. Novel therapies are therefore urgently needed to improve outcomes in this challenging patient population. It has previously been shown that Wnt/β-catenin signaling is active in GCTs suggesting that its inhibitors LGK974 and PRI-724 may show promise in the management of cisplatin-refractory GCTs. We herein investigated whether LGK-974 and PRI-724 provide a treatment effect in cisplatin-resistant GCT cell lines. Taking a genoproteomic approach and utilizing xenograft models we found the increased level of β-catenin in 2 of 4 cisplatin-resistant (CisR) cell lines (TCam-2 CisR and NCCIT CisR) and the decreased level of β-catenin and cyclin D1 in cisplatin-resistant NTERA-2 CisR cell line. While the effect of treatment with LGK974 was limited or none, the NTERA-2 CisR exhibited the increased sensitivity to PRI-724 in comparison with parental cell line. Furthermore, the pro-apoptotic effect of PRI-724 was documented in all cell lines. Our data strongly suggests that a Wnt/β-catenin signaling is altered in cisplatin-resistant GCT cell lines and the inhibition with PRI-724 is effective in NTERA-2 CisR cells. Further evaluation of Wnt/β-catenin pathway inhibition in GCTs is therefore warranted.
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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.