Cell Line Panel Profiling for Discovery of Multiple Myeloma Therapeutics

Project Summary Drug combination therapy has revolutionized cancer treatment and is now the mainstay of most modern regimensIn spite of the successit is evident that in most casesthe cancer either does not respond to the initial treatment or a form of the cancer emerges that is cross resistant to multiple drugsInvestigation 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 firstline chemotherapeutic cocktailsHowever in most indicationsonly a small minority of the patients respond to the drug and resistance emerges rapidly resulting in new therapies with limited clinical benefitAlthough targeted therapies have significant limitations as single agentstheir unique targets and limited side effect profiles present a growing opportunity for more effective treatments using combination therapiesIt has been shown that targeted therapies can act synergistically by targeting the same pathwaya complementary pathway or alter signaling feedback loops that enhance signalingThusin order to define novel combination therapiesit is necessary to define how the drugs interact with the cellular machinery through the definition of drug signaturesHoweverthis is generally not possible with existing technologiesThe goal of this Phase II SBIR is to create a system that can monitor more thansignaling events incell lines simultaneously for the high throughput generation of drug signaturesUsing this discovery tool it will be possible to explore drug synergy with the detail necessary to identify novel advantageous combinations