Probing the Interrelationship of Microvascular Structural Adaptation, Vessel Co-Option, and Resistance to Anti-Angiogenesis Therapy in Micro-Engineered Vessels

ASPIRE Award

Tumor angiogenesis – the ability for tumors to grow a new blood supply – is a target for anti-tumor therapies. However, tumors become resistant to anti-angiogenesis drugs within weeks or months. This may be because, rather than just forming new blood vessels, tumors can instead co-opt blood vessels from surrounding tissue causing angiogenesis inhibitors to become ineffective at impeding tumor growth and metastasis. The mechanisms behind co-option are currently not understood, and it has been hypothesized that the anti-angiogenesis drug, bevacizumab, could actually render blood vessels more susceptible to co-option. To probe the biology of blood vessel co-option by tumors, Dr. Jonathan Song and his team at The Ohio State University are creating a microfluidic disease model of vessel co-option to determine the molecules that mediate this process and how resistance to anti-angiogenesis therapy occurs. Their model consists of a microvascular lumen made from endothelial cells embedded in a three-dimensional extracellular matrix with cancer cells positioned to carry out vessel co-option. This model will allow the team to observe the process as it occurs. Using this model, they will gain insights into the mechanism of vessel co-option and study how the process differs in tumors treated with anti-angiogenesis drugs. Their work will help uncover new therapeutic targets for blocking the access of cancer cells to a blood supply thereby inhibiting tumor growth.