Cell Line Panel Profiling for Discovery of Multiple Myeloma Therapeutics

项目摘要 药物联合治疗已经彻底改变了癌症治疗，现在是大多数癌症治疗的支柱。 现代养生法尽管取得了成功，但很明显，在大多数情况下， 对最初的治疗没有反应，或者出现了交叉耐药的癌症形式 多种药物。研究癌症的分子原因和戏剧性的改善 药物发现过程中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种药物耐药的患者有效， 线化疗鸡尾酒。然而，在大多数适应症中， 患者对药物有反应，耐药性迅速出现，导致新的治疗方法， 临床获益有限。尽管靶向治疗作为单一药物具有显著的局限性， 他们独特的目标和有限的副作用概况提供了越来越多的机会， 使用联合疗法的有效治疗。有证据表明，靶向治疗 可以通过靶向相同途径、互补途径或改变 增强信令的信令反馈回路。因此，为了定义新颖的组合， 治疗时，有必要确定药物如何与细胞机制相互作用， 药物特征的定义然而，这在现有的情况下通常是不可能的。 技术.第二阶段SBIR的目标是创建一个系统， 在10个细胞系中同时发生100个信号传导事件，用于高通量产生药物 签名.使用这种发现工具，将有可能探索药物协同作用的细节 需要识别新的有利组合。

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.