Host microenvironment dictates tumor growth, angiogenesis and vascular permeability

Abstract

With new potential therapies for the treatment of human solid tumors constantly arising, the need for a suitable animal model which is clinically relevant becomes critical. An important criterion in the treatment of solid tumors is the understanding of the molecular and microenvironmental events that influence tumor formation, growth, metastasis and vascularization. Here we develop new tumor models that appear to more accurately depict human tumors in many ways beyond the standard subcutaneous models used predominately in the past. When we tested orthotopic, subcutaneous as well as non‐orthotopic engrafted tissues it was still clear that the orthotopic models provided a microenvironment more suitable for tumor growth and angiogenesis as well as being more restrictive. It may not be surprising with this pervasive vascular leakiness in the subcutaneous tumor models enable many treatments to work preclinically. But unfortunately this does not translate in clinical trials in humans. We are in the process of testing clinical drugs in our model. Here we show evidence that the host microenvironment plays an important role in tumor growth, angiogenesis and vascular permeability. Therefore, we feel this "pseudo‐ectopic/orthotopic" method may be more clinically relevant for testing potential therapies for the treatment of both primary and metastatic human solid tumors.