navitoclax + irinotecan

**Navitoclax + irinotecan** is an investigational combination therapy composed of navitoclax, an oral small molecule inhibitor of anti-apoptotic Bcl-2 family proteins (including Bcl-2 and BCL-xL), and irinotecan, a topoisomerase I inhibitor used as chemotherapy. Navitoclax promotes apoptosis by inhibiting Bcl-2 family proteins, thereby lowering the apoptotic threshold in cancer cells, while irinotecan induces DNA damage by inhibiting topoisomerase I, leading to cell cycle arrest and cell death. Preclinical studies show that navitoclax enhances the antitumor efficacy of irinotecan in several solid tumors (colon, gastric, pancreatic, small cell lung cancer)[5], and early clinical data suggest the combination is active in heavily pretreated patients with advanced malignancies[1][5][7]. The combination has also shown therapeutic benefit in fibrolamellar hepatocellular carcinoma (FLC) models[3].