Cancer

Cell culture and mouse studies suggest inhibiting CPT1A alone or in combination with VEGF inhibition could help treat hepatocellular carcinoma and colorectal cancer. In a mouse colorectal cancer cell line cultured under low oxygen conditions associated with VEGF inhibitor treatment, the CPT1A inhibitor etoxomir decreased proliferation compared with no treatment. In mouse models of hepatocellular carcinoma and colon cancer, tumor-specific shRNA-mediated knockdown of CPT1A plus an anti-VEGF mAb decreased tumor size and tumor cell proliferation and increased tumor cell apoptosis compared with the anti-VEGF mAb alone. In the colon cancer model, etoxomir decreased tumor size and tumor cell proliferation and increased tumor cell apoptosis compared with no treatment, and etoxomir plus the anti-VEGF mAb decreased tumor cell proliferation and increased tumor cell apoptosis compared with either agent alone. Next steps could include testing additional CPT1A inhibitors alone or in combination with VEGF inhibition in the models.

In 2002, Medigene AG discontinued Phase II testing of etoxomir for congestive heart failure...