Radiation insensitive tumors that become radiation resistant are often also invasive, metastatic, and responsible for most cancer deaths. Here, the long term objective is to complete clinical evaluation of an inhibitor of a new target (V-ATPase) that sensitizes tumors but not healthy tissues to radiation and inhibits multiple aspects of tumor metabolism and therapeutic resistance. Development of the inhibitor begins with its preparation and determination of its lifetime in cell culture media and in preparation of stable, concentrated dosing solutions suitable for continuous infusion. Next, it will be determined if that SaliPhe and SaliPhe plus ionizing radiation (IR) are much more toxic to a panel of non-small cell lung cancer (NSCLC) cell lines, than to a panel of normal human bronchial epithelial cells (HBEC). To probe the mechanisms of the differences, genomic expression studies and metabolism studies will be performed on untreated cells of both panels and treated with SaliPhe and with SaliPhe + IR. From these data, two NSCLC cell lines will be evaluated in tumor models where the effect of SaliPhe alone, IR, and SaliPhe+ IR are observed. Compelling data will propel further development of SaliPhe as a radiation sensitizer and plan set forth for further development and commercialization.
