Rationales for Combining Therapies to Treat Cancer: Independent Action, Response Correlation, and Collateral Sensitivity Versus Synergy

The principle of independent drug action proposes that responses to combinations result from one or the other two combining agents, but not both. Explorations biological pathway interactions in signal transduction and immunobiology as synergy have been connected mathematical demonstrations above–independent activity, which would define pharmacologic synergy. We review explanation for cancer find no evidence Rather, a measure correlation response ( ρ) when positive can explain below–independent results, negative results. Anticorrelated may be demonstration collateral sensitivity, achieve activity. Inappropriate use concepts contributing high failure rates immuno-oncology clinical trials, indicating need more rigorous applications development combination therapy.