Cell Line Panel Profiling for Discovery of Multiple Myeloma Therapeutics

项目摘要 药物联合疗法给癌症治疗带来了革命性的变化，现在是大多数 现代养生法。尽管取得了成功，但很明显，在大多数情况下，癌症或 对最初的治疗没有反应，或者出现了一种交叉耐药的癌症 与多种药物有关。癌症分子病因的研究和重大进展 已经创造了一类新的分子靶向药物 已被证明对无反应或对第一次有抵抗力的患者有效 一线化疗鸡尾酒。然而，在大多数迹象中，只有一小部分 患者对药物有反应，耐药性迅速出现，导致新的治疗方法 临床益处有限。尽管靶向治疗作为单一药物有很大的局限性， 他们独特的靶点和有限的副作用特征提供了越来越多的机会 使用综合疗法的有效治疗。有研究表明，靶向治疗 可以通过针对相同的途径、互补的途径或改变来协同作用 增强信令的信令反馈循环。因此，为了定义小说组合 对于治疗，有必要定义药物如何通过 药物签名的定义。但是，这通常不可能使用现有的 技术。此第二阶段SBIR的目标是创建一个能够监控超过 在10个细胞系中同时发生100个信号事件，以实现药物的高通量产生 签名。使用这一发现工具，将有可能探索药物协同与细节 对于确定新的有利组合是必要的。

Project Summary Drug combination therapy has revolutionized cancer treatment and is now the mainstay of most modern regimens. In spite of the success, it is evident that in most cases, the cancer either does not respond to the initial treatment or a form of the cancer emerges that is cross-resistant to multiple drugs. Investigation into the molecular causes of cancer and dramatic improvements to the drug discovery process have created a new class of molecularly targeted agents that have proven to be effective in patients that are non-responsive or have become resistant to first- line chemotherapeutic cocktails. However in most indications, only a small minority of the patients respond to the drug and resistance emerges rapidly resulting in new therapies with limited clinical benefit. Although targeted therapies have significant limitations as single agents, their unique targets and limited side effect profiles present a growing opportunity for more effective treatments using combination therapies. It has been shown that targeted therapies can act synergistically by targeting the same pathway, a complementary pathway or alter signaling feedback loops that enhance signaling. Thus, in order to define novel combination therapies, it is necessary to define how the drugs interact with the cellular machinery through the definition of drug signatures. However, this is generally not possible with existing technologies. The goal of this Phase II SBIR is to create a system that can monitor more than 100 signaling events in 10 cell lines simultaneously for the high-throughput generation of drug signatures. Using this discovery tool it will be possible to explore drug synergy with the detail necessary to identify novel advantageous combinations.