Tumor anatomy can be described using a three compartment model including the tumor vasculature, the interstitial space and the actual neoplastic cells . For any systemically administered anti-neoplastic chemotherapeutic to have clinical efficacy it must first circulate through the systemic vasculature, exit from the intratumoral vascular space, traverse the interstitium and enter or effect the neoplastic cell in large enough quantities to have efficacy. At each of these steps there are barriers, related to tumor anatomy and physiology, which hinder delivery of the drug throughout the entire tumor [2-4]. Poor efficacy of promising therapeutics may be attributable to these barriers. A multitude of promising strategies have been described to circumvent these barriers including targeted therapeutics and intratumoral delivery. These exploratory approaches, in various stages of development, may likely supplant current systemic chemotherapeutic administration. While theoretically efficacious, no approach is broadly validated or accepted at this early stage of a probable paradigm shift.
Monsky WL (2012) Circumventing Anatomic and Physiologic Barriers to the Intratumoral Delivery of Therapeutics. Anatom Physiol 2:e114.