Side effects of molecularly targeted drugs and their molecular mechanisms

Abstract

Molecularly targeted therapy has become widely used in clinical settings over the last decade. Although it was initially expected that molecularly targeted drugs have fewer side effects, it is becoming increasingly apparent that molecularly targeted drugs have an unanticipated repertoire of side effects. Some side effects are serious, some are manageable, some are rare, and some are frequent. Some may affect individuals with predisposing factors. In this minireview, we briefly summarize how the side effects of molecularly targeted drugs were discovered when new classes of drugs were introduced. We also summarize the clinical characteristics of these side effects focusing on progressive multifocal leukoencephalopathy (PML) associated with the use of an integrin antagonist, cardiotoxicity associated with the use of some tyrosine kinase inhibitors, and hypertension associated with the use of angiogenesis inhibitors. We also review the molecular mechanisms underlying these side effects. Research on the mechanisms underlying these side effects has revealed previously unknown physiological roles of targetedmolecules. Awareness and understanding of the side effects of molecularly targeted drugs is important for those working in clinical practice and conducting basic research.