Final Report Summary - REENGINEERINGCANCER (Re-engineering the tumor microenvironment to alleviate mechanical stresses and improve chemotherapy)
During the implementation of the ERC funded project, ReEngineeringCancer, a mathematical modeling framework was developed to predict the growth of tumors and their response to chemotherapy. The model takes into consideration the functionality of the tumor vasculature that supplies with nutrients and oxygen the tumor but also delivers the chemotherapeutic agent to cancer cells. The functionality of the tumor vasculature is compromised because it is affected by the accumulated mechanical forces within a tumor as the tumor grows at the expense of the surrounding normal tissue. These intratumoral mechanical forces can compress blood vessels and exclude regions of the tumor from blood supply and thus, delivery of drugs. The model predicted the conditions under which alleviation of these forces can be achieved so that blood vessels will decompress, regain their functionality and deliver more effectively drugs to the tumor. Furthermore, experiments in mice bearing breast tumors were performed to validate model predictions and provided a proof of principle of the stress alleviation strategy. Specifically, it was found that the combinatorial treatment of tumors with a common anti-fibrotic drug to alleviate mechanical stresses and improve vessel functionality and with a chemotherapeutic drug to eradicate cancer cells enhances the efficacy of chemotherapy in breast and pancreatic preclinical tumor models.