Revisiting Antiangiogenic Multikinase Inhibitors in the Era of Immune Checkpoint Blockade: The Case of Sorafenib

The successful development of multikinase inhibitors over the last two decades has revolutionized the management of many malignant cancers. Agents such as the antiangiogenic kinase inhibitor sorafenib have certain advantages such as a broad spectrum of activity against cancer cells, vascular endothelial cells, and pericytes, and are the mainstay of treatment in diseases such as advanced renal or liver cancer. The more recent emergence of immunotherapy—using immune checkpoint blockade—in some of the same diseases has raised important questions about the treatment interaction with antiangiogenic drugs, seven such combinations have been approved for lung, liver, kidney, and endometrial cancers, and multiple combination therapies are being aggressively pursued in the clinic. Thus, revealing mechanisms of action of antiangiogenic kinase inhibitors in combination with immune checkpoint blockade is critical to improving the treatment outcome further. This Landmark commentary on sorafenib in cancer therapy highlights these important questions.