Metastatic clear cell renal cell carcinoma remains a high unmet medical need, as almost all patients develop resistance to the standard of care. Whole-genome sequencing (WGS) has identified a prevalence of activating mutations in NOTCH1 in metastatic ccRCCs. In a recent study by Bui et al., titled “Metastatic clear-cell renal cell carcinoma: a frequent NOTCH1 mutation predictive of response to anti-NOTCH1 CB-103 treatment” the authors have shown that CB-103 eliminates NOTCH mutated clones, induces necrosis, exhibits anti-angiogenic activity, and thereby inhibits tumor growth in PDX models of metastatic ccRCC. This independent study supports the clinical development of CB-103 in metastatic clear cell renal cell carcinoma.
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