Strategies to improve drug distribution in solid tumor

Most research on the resistance of cancers to chemotherapy has concentrated on molecular mechanisms of resistance, whereas the role of limited drug distribution within tumors has been neglected. One critical obstacle to the success of anticancer therapies, especially to chemotherapy, radiotherapy and immunotherapy, is related to the inefficient distribution of drugs or oxygen to cancer cells. To be most effective anticancer drugs must penetrate tissue efficiently, reaching all the cancer cells that comprise the target population in a concentration sufficient to exert a therapeutic effect. The causes of the inefficient distribution of the anticancer compounds in the tumor bulk are multiple and interconnected. Obviously, the penetration capacity of a drug depends on its physicochemical properties, but the reasons for low delivery can be mainly ascribed to the tumor microenvironment, such as absent or immature vessels, irregular blood flow, high interstitial fluid pressure (IFP), low oxygen (hypoxia) and high acidity. In this article, we discuss the potential strategies to improve the drug distribution by modifying factors such as tumor vessels, tumor blood flow, tumor stroma, tumor cells, interstitial fluid pressure (IFP), and drug properties.