IGF::OT::IGF DEVELOPMENT OF A VATPASE INHIBITOR AS A RADIOSENSITIZER

变得耐辐射的辐射不敏感肿瘤通常也是侵袭性的、转移性的，并且是大多数癌症死亡的原因。在这里，长期目标是完成对新靶点（V-ATP酶）抑制剂的临床评价，该抑制剂使肿瘤而不是健康组织对辐射敏感，并抑制肿瘤代谢和治疗耐药性的多个方面。 抑制剂的开发始于其制备和测定其在细胞培养基中的寿命，以及制备稳定的浓缩给药溶液， 用于连续输注。接下来，将确定SaliPhe和SaliPhe加电离辐射（IR）是否对一组非小细胞肺癌（NSCLC）细胞系毒性更大， 而不是一组正常的人支气管上皮细胞（HBEC）。为了探索差异的机制，将对以下进行基因组表达研究和代谢研究： 根据这些数据，将在肿瘤模型中评估两种NSCLC细胞系，其中单独的SaliPhe、IR和IR对两种细胞系的作用是相同的。 观察到SaliPhe+ IR。令人信服的数据将推动SaliPhe作为辐射敏化剂的进一步开发，并计划进一步开发和商业化。

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.