Improving drug penetration to curb tumor drug resistance

Several classes of drugs that we refer to here as ‘promoter drugs’ can improve tumor uptake and penetration of other drugs that we refer to as ‘effector drugs’, which exert direct antitumor effects. In this review we discuss the main therapeutic advantages that can be obtained by using promoter drugs. First, tumor-specific enhancement of effector drug accumulation but unaltered accumulation in normal tissues with improvement of the therapeutic index. Second, we propose that curbing tumor drug resistance is another important consequence of using promoter drugs. In particular, we discuss evidence suggesting that promoter drugs can (i) prevent induction of new resistance by paracrine factors released in response to effector drugs, and (ii) reverse existing drug resistance induced by mechanical cues and tumor-cell–extracellular-matrix interactions.

► Improving tumor penetration of antitumor drugs enhances the therapeutic index. ► It may prevent also drug resistance caused by drug-induced paracrine factors. ► It may reverse drug resistance of tumors induced by mechanical cues. ► It may reverse drug resistance induced by tumor cell-stroma interactions.