ArticleExperimental hematology & oncology2023
Metastatic clear-cell renal cell carcinoma: a frequent NOTCH1 mutation predictive of response to anti-NOTCH1 CB-103 treatment.
Article in Experimental hematology & oncology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers, 1 of them a synthesis that pooled it.
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Who cites it
5 citing papers in PubMed, 1 synthesis or guideline pooled it, 3 citations in OpenAlex.
- Genomics of Primary and Metastatic Cutaneous Melanoma: A Systematic Review and Meta-Analysis.American journal of clinical dermatology · 2026Pooled it
- ETS1-EGR2 facilitates renal cell carcinoma progression by activating NOTCH signalling.Clinical and translational medicine · 2026Article
- Prognostic Significance of NOTCH1-ICD Expression in Renal Cell Carcinoma.Journal of kidney cancer and VHL · 2026Article
- Circulating tumour cell clusters: isolation, biological significance and therapeutic implications.BMJ oncology · 2024Review
- Modulation of Notch Signaling by Small-Molecular Compounds and Its Potential in Anticancer Studies.Cancers · 2023Review
Corrections and comments
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Authors and funding
15 authors at 5 institutions in 2 countries.
Funding
Abstract
backgroundClear-cell renal cell carcinomas (ccRCCs) are malignant tumors with high metastatic potential and resistance to treatments occurs almost constantly. Compared to primary tumors, there are still limited genomic data that has been obtained from metastatic samples.
methodsWe aimed to characterize metastatic ccRCC by way of whole-genome analyses of metastatic formalin-fixed samples, using OncoScan
resultsWe showed that pL1575P NOTCH1 mutation was an activating mutation, leading to the expression of NOTCH1-intracellular domain-active fragments in both cancer cells and tumor endothelial cells, suggesting a trans-differentiation of cancer cells into tumor micro-vessels. We demonstrated that this mutation could be used as a predictive biomarker of response to CB-103, a specific NOTCH1-intracellular domain inhibitor. One striking result was the considerable anti-angiogenic effect, coherent with the presence of NOTCH1 mutation in tumor micro-vessels.
conclusionsWe identified a frequent, unexpected pL1575P_c4724T_C NOTCH1 mutation as a new biomarker for ccRCC metastases, predictive of response to the CB103 NOTCH1-intracellular domain inhibitor.
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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 OpenQuestion graph.