How to improve exposure of tumor cells to drugs: promoter drugs increase tumor uptake and penetration of effector drugs.

Solid tumors are characterized by an abnormal architecture and composition that limit the uptake and distribution of antitumor drugs. Over the last two decades, drugs have been identified that improve the tumor uptake and distribution of drugs that have direct antitumor effects. We propose to refer to these drugs as promoter drugs, and as effector drugs to drugs that have direct antitumor effects. Some promoter drugs have received regulatory approval, while others are in active clinical development. This review gives an overview of promoter drugs, by classifying them according to their mechanism of action: promoter drugs that modulate tumor blood flow, modify the barrier function of tumor vessels, induce tumor cell killing, and overcome stromal barriers. Eventually, we discuss those that we feel are the main conclusions to be drawn from promoter drug research that has been performed so far, and suggest areas of future investigation to improve the efficacy of promoter drugs in cancer therapy.