Two paradigms for small molecule–targeted therapies in cancer. (A) In the recurrent mutation model exemplified by CML, selective inhibition of a kinase with recurrent mutation or translocation leads to direct cell death. (B) In the functional model as seen in CLL, kinase inhibition disrupts the prosurvival signals from the BCR and the microenvironment, leading to de-adhesion of malignant cells from the microenvironment and subsequent cell death in the peripheral blood. Professional illustration by Marie Dauenheimer.