Mammary Neoplasms, Human

All mouse studies were approved by the Institutional Animal Care and Use Committee at The University of Texas MD Anderson Cancer Center. K-ras^LSL-G12D mice were purchased (Jackson Laboratories). 129/SV syngeneic mice and nu/nu mice were bred in-house. Mice received standard care and were euthanized according to the standards set forth by the Institutional Animal Care and Use Committee. To generate autochthonous lung tumors, 50,000 GFP-Cre or PI4KB-cre lentivirus particles were delivered into the lungs of K-ras^LSL-G12D mice through an endotracheal tube as reported previously (34 (link)). As we have described (59 (link)), KP cells were injected subcutaneously (10⁶ cells) or intravenously (10⁵ cells) into syngeneic, immunocompetent mice, and human lung cancer cells were injected intrathoracically (10⁶ cells) into nu/nu mice. Mice bearing human H2122 or H23 orthotopic lung tumors were treated with compound A (100 mg/kg) or vehicle (5% DMSO, 20% HPBCD, 2% Poly 80, and 10% PEG300) twice daily by intraperitoneal injection beginning 21 d after tumor cell injection and continued for 7 d. Nu/nu mice bearing human MB-MDA-468 breast tumors or lung cancer patient-derived xenografts were treated for 7 d with vehicle or compound A once tumors reached 100 mm³. Nu/nu mice bearing human H2122 orthotopic lung tumors were treated with compound B (20 mg/kg or 40 mg/kg plus 20 mg/kg ritonavir) or vehicle (5% DMSO, 20% HPBCD, 2% Poly 80, and 10% PEG300) subcutaneously twice daily beginning 7 d after tumor cell injection and continued for 21 d. For each model, necropsies were performed to quantify primary tumor size and metastatic tumor burden.