Penetration of anticancer drugs through solid tissue: a factor that limits the effectiveness of chemotherapy for solid tumors

Abstract

Penetration of anticancer agents to cells distant from the vascular system is required for efficacy of cancer chemotherapy against solid tumors. Many solid tumors have a poorly formed blood vascular system with variable rates of blood flow and much larger intercapillary distances than those found in normal tissues. The requirement for drugs to penetrate several layers of tissue might pose a barrier to the effective treatment of solid tumors. Multicellular layers (approximately 200 microm thick) were grown in vitro on Teflon membranes from EMT6 murine and MCF7 human tumors and have been used to quantitate the penetration of four widely used anticancer drugs through solid tissue. The penetration of doxorubicin and mitoxantrone was limited and very slow (<10% of the rate of penetration through the Teflon membrane alone). The penetration of methotrexate and 5-FU was more rapid (approximately 30-50% of the rate of penetration through the Teflon membrane alone), but remains a substantial barrier to the effectiveness of these drugs. Strategies to improve the penetration of anticancer drugs through poorly vascularized tumor tissue have considerable potential to improve the outcome of chemotherapy for solid tumors.