Selection of targets and novel agents in early clinical trials of CLL. There are multiple “biological” therapeutic approaches in current clinical development in CLL. Signal transduction inhibition will often target the B-cell receptor cascade, which has been shown to be critical to CLL cell survival. A number of surface molecules of CLL cells can be targeted by antibodies. Different members of the apoptosis machinery are targets currently explored in clinical trials. Microenvironmental stimulation and T-cell interaction are of critical importance for CLL cell survival, and are being increasingly utilized for treatment strategies. There is ongoing interest in using mutant p53 as a “druggable” target, and a number of agents have been identified that may preferentially target mutant p53.34 Improving efficacy in CLL with p53 pathway defects is likely to offer the greatest overall benefit.
