Synergistic Drug Combinations Provide Better Outcomes for Cancer Patients
September 22, 2010 1 Comment
Among the most sought after attributes of chemotherapy drug combinations is drug synergy. Synergy, defined as supra-additivity wherein the whole is greater than the sum of the parts, reflects an elegant interaction between drugs predicated on their modes of action. While some synergistic interactions can be predicted based upon the pharmacology of the agents, others are more obscure.
We have extensively examined the synergy between classes of drugs based on known modes of action. But, in some circumstances, our studies have been purely exploratory. Among our most successful findings have been:
- Alkylating agent plus purine analogs (cytoxan & fludarabine)
- Platin plus antimetabolites (cisplatin & 5FU; cisplatin & gemcitabine)
- Dual antimetabolite combinations (gemcitabine & capecitabine)
- Natural products plus anti-metabolite (Doxil & gemcitabine; vinorelbine & capecitabine)
More recently, we have explored the interaction between signal transduction inhibitors. The results of these investigations have been the subject of numerous presentations at international meetings.
The application of synergy analyses may represent one of the most important applications of our functional profiling platform; enabling us to explore both anticipated and unanticipated favorable interactions. Equally important may be our capacity to study drug antagonism wherein two effective drugs counteract each others’ benefits. This phenomenon, characterized by the whole being less than the sum of the parts, represents a major pitfall for clinical trialists who simply combine drugs “because they can.”
These analyses are revolutionizing the way our group applies newer classes of drugs and has the potential to accelerate drug development and clinical therapeutics. Good outcomes require good drugs, but better outcomes require good combinations. Intelligent combinations are a principle focus of the work at Rational Therapeutics. We strive everyday to identify the best outcomes for patients.