"Over the last 5 decades particle beam cancer therapy has shown its potential advantages in targeting tumors in critical areas. Multiple centers have been established around the world. To date about 60,000 patients have been treated with protons and 4000 patients have received heavy ion treatments. Despite the apparent success of these treatments a continued effort is necessary to provide the best possible therapeutic ratio – the ratio of the biological effective dose to the tumor compared to biological effect to normal tissue. Antiprotons have a significant advantage in this respect through the annihilation at the end of range. This annihilation event doubles the local energy deposition compared to protons and in addition delivers this dose in form of heavy ion recoils that exhibit an enhanced biological effect. A third advantage is the possibility of real-time imaging of the dose delivery process through detection of high-energy annihilation products. Especially in the case of radio-resistant tumors in close proximity of critical organs and structures, these advantages could provide the crucial difference between success and failure. We propose to firmly establish the biological advantages of antiprotons through a multitude of experiments using different cell lines and biological endpoints including clonogenic survival, genetic expressions, DNA modifications, to not only discern the potential tumor control but also to judge potential long term effects due to low dose delivery to normal tissue caused by secondary particles. Through this work we will generate the necessary input data to develop and benchmark a treatment planning system capable of generating comparative treatment plans for antiprotons and other external radiation therapy modalities. Using this treatment planning system we will identify a list of cases where the enhancement available through antiprotons can truly make a decisive difference."