Multidrug resistance in cancer therapy: role of the microenvironment.

Despite advances in the design of chemotherapeutic agents, and although many of these effective agents are now available for clinical use, most human cancers are resistant to therapy at presentation or become resistant after an initial response. The effectiveness of chemotherapy is compromised by several microenvironmental factors that affect the bioavailability and efficacy of chemotherapeutic agents. These factors vary from one tumor to another, and from one location to another, within the same tumor. A better comprehension of microenvironmental multidrug resistance mechanisms would lead to a clearer understanding of the reason for chemotherapeutic failure. This improved knowledge will permit a more rational utilization of chemotherapy.