You Cannot Have Your Synergy and Efficacy Too

Synergistic drugs are preferred in combination therapies for many diseases, including viral infections and cancers. Maximizing synergy, however, may come at the cost of efficacy. This synergy-efficacy trade-off appears to be widely prevalent and independent of the specific drug interactions yielding synergy. We present examples of the trade-off in drug combinations used in hepatitis C, HIV, and cancer therapies and believe that screens for optimal drug combinations that presently seek to maximize synergy may be improved by considering the trade-off.