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Cabozantinib + CB-839 is a combination of two small molecule drugs under investigation for cancer treatment, primarily in metastatic renal cell carcinoma (RCC) and neuroendocrine tumors (NETs). **Cabozantinib** is a tyrosine kinase inhibitor that targets multiple kinases, notably **VEGFR2, MET, and AXL**, which are key drivers of tumor growth, metastasis, and angiogenesis. **CB-839** (also known as **telaglenastat**) is an oral, selective inhibitor of **glutaminase**, an enzyme crucial for cancer cell metabolism, particularly in tumors that are dependent on glutamine for proliferation and survival. By combining these agents, the regimen aims to disrupt complementary oncogenic pathways: inhibiting both key tyrosine kinases and tumor cell metabolism. Preclinical and early clinical studies have shown that this combination can be synergistic in renal cell and neuroendocrine tumor models. However, large clinical trials to date have not shown a significant improvement in progression-free survival over cabozantinib monotherapy in metastatic RCC, though the combination is generally well tolerated.
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