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Sorafenib + irinotecan is a combination therapy of two small molecule drugs used primarily in oncology. Sorafenib is a multikinase inhibitor that targets serine/threonine kinases Raf-1 and B-Raf, as well as receptor tyrosine kinases including vascular endothelial growth factor receptor 1 (VEGFR1), vascular endothelial growth factor receptor 2 (VEGFR2), and vascular endothelial growth factor receptor 3 (VEGFR3) and platelet-derived growth factor receptor beta (PDGFRB). This results in inhibition of tumor cell proliferation and angiogenesis. Irinotecan is a topoisomerase I inhibitor; it blocks the enzyme DNA topoisomerase I, leading to DNA damage during replication and ultimately cancer cell death[2][6]. The combination has shown synergistic antitumor activity, particularly in KRAS-mutated metastatic colorectal cancer (mCRC), with clinical trials demonstrating disease control rates up to 65% in heavily pretreated patients[2][4][8]. It has also been studied for advanced hepatocellular carcinoma (HCC) and pediatric solid tumors[1][3].
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