Targeting Inflammation to Improve Tumor Drug Delivery

Abstract

Inefficient delivery of drugs is a main cause of chemotherapy failure in hypoperfused tumors. To enhance perfusion and drug delivery in these tumors, two strategies have been developed: vascular normalization, aiming at normalizing tumor vasculature and blood vessel leakiness, and stress alleviation, aiming at decompressing tumor vessels. Vascular normalization is based on anti-angiogenic drugs, whereas stress alleviation is based on stroma-depleting agents. We present here an alternative approach to normalize tumor vasculature, taking into account that malignant tumors tend to develop at sites of chronic inflammation. Similarly to tumor vessel leakiness, inflammation is also characterized by vascular hyperpermeability. Therefore, testing the ability of anti-inflammatory agents, such as non-steroidal anti-inflammatory drugs (NSAIDs) or inflammation resolution mediators, as an alternative means to increase tumor drug delivery might prove promising.

Keywords: anti-inflammatory agents; inflammation resolution; stress alleviation; tumor perfusion; vascular normalization.

Figure 1. Key Figure: Main strategies to improve drug delivery to tumors.

Stress alleviation decompresses tumor blood vessels by targeting tumor ECM (desmoplasia); whereas vascular normalization reduces tumor vessel wall permeability. Both strategies can improve perfusion and drug delivery. Anti-inflammatory treatment is proposed as an alternative to anti-angiogenic treatment to induce vascular normalization.