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Sonidegib + nilotinib is an **experimental oral combination therapy** of two small molecules: sonidegib, a selective smoothened (SMO) antagonist that inhibits the Hedgehog signaling pathway, and nilotinib, a BCR-ABL tyrosine kinase inhibitor primarily used in chronic myeloid leukemia (CML). This combination was investigated to overcome resistance to prior BCR-ABL tyrosine kinase inhibitors in Philadelphia chromosome-positive CML, leveraging potential effects on both cancer cell survival signals (via Hedgehog pathway) and tyrosine kinase-driven proliferation. The regimen was explored in clinical trials for patients with chronic or accelerated phase CML who had failed previous TKI therapies. However, clinical trials were terminated early due to lack of efficacy and tolerability issues, and no evidence of clinical benefit over nilotinib alone was observed[1][3][5].
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