BIOMEDICAL (BASIC)

肿瘤抑制因子p53的失活或应激反应蛋白（例如NF-κ B或HSF-1和其他热休克蛋白）的组成性激活经常在许多类型的癌症中发现。这种变化通常与化疗反应差有关，因此，生存率降低。Curaxins是一类新型的多功能抗肿瘤药物，同时针对所有这三个途径。比较肿瘤中Curaxins的疗效和蓄积将使我们能够优先考虑这些药物（例如，对耐药肿瘤最有效的药物首选铅）。这一提议的意义在于我们的化合物能够同时靶向通常与治疗反应不良相关的多个途径，因此对许多癌症类型具有广泛的适用性。

Inactivation of the tumor suppressor p53 or constitutive activation of stress response proteins (e.g. NF-kB or HSF-1 and other heat shock proteins) are frequently found in many types of cancers. Such changes are often associated with poor response to chemotherapy and, thus, decreased survival. Curaxins are a novel class of multifunctional antitumor agents that simultaneously target all three of these pathways. Comparison of the efficacy and accumulation of Curaxins in tumors will enable us to prioritize these drugs (e.g. most effective against resistant tumors preferable for lead). The significance of this proposal lies in the ability of our compounds to simultaneously target multiple pathways frequently associated with poor treatment response and thus has broad applicability to many cancer types.