What are the reasons for negative phase III trials of molecular‐target‐based drugs?

The results of molecular‐biological studies of cancer are changing the way we diagnose and treat cancer. Target‐based drug discovery selects agents for development based on their mechanisms of action. The interaction between target‐based drugs and their targets can be described by classical drug‐receptor theory. Clinical trials have demonstrated that some effective target‐based drugs induce apoptosis, even though they are considered to be cyto‐static. Numerous phase III trials of target‐based drugs have been conducted. Although some have yielded strongly positive results, the majority of the results have been negative. This article seeks to clarify the value of molecular‐target‐based therapy and to discuss the reasons for negative results in phase III trials. The importance of proof‐of‐principle studies is stressed throughout preclinical and clinical trials of molecular‐target‐based drugs.