Targeting immunosupportive cancer therapies: accentuate the positive, eliminate the negative

In this Commentary we aim to provide an overview of some specific examples of cancer therapeutics, including targeted approaches using monoclonal antibodies and kinase inhibitors, as well as highlight novel approaches for enhancing immunological responses against tumors. We point out that a fundamental property of the cancer cell, genomic instability, confounds the targeted therapies that aim to induce cell death directly while simultaneously enhancing the potential for immunological attack by creating a large number of neoantigens. We argue for combinatorial strategies with agents that target tumor cells to release these antigens together with innovative therapies that enhance immunological responses by interfering with inhibitory checkpoints.