Tumor Tight Junction Opener + Chemotherapy Conjugates to Treat Cancer

Project Summary Tumors survive cancer therapy in part by blocking the entrance and permeation of drugs into the cancer. We have developed a therapeutic, JO-1 , that selectively opens up tumors, which dramatically enhances penetration. This results in markedly increased concentrations of cancer drugs in the tumor, which becomes a sink , thereby reducing drug levels in the rest of the body. JO-1 may allow doctors to treat patients with cancer drugs at increased doses, which directly correlates with enhancedtherapeutic effects. At the same time, it could reduce or eliminate the side effects of cancer therapy and address one of the major needs of the current state-of-the- art: Developing therapies that are both more effective and less toxic. Importantly, JO-1can be used to improve clinical outcomes with cancer drugs that are already on the market as well as the next generation of cancer drugs. The goal of this proposal is to develop and test a new Targeted / Enhancing Conjugate ( TEC ) of a tumor-targeting t