Penetration of Anticancer Drugs through Solid Tissue: A Factor That Limits the Effectiveness of Chemotherapy for Solid Tumors

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 (∼200 μm 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 (