Targeted drugs in oncology: New names, new mechanisms, new paradigm

Abstract

The molecular mechanisms of action, clinical development, and efficacy and safety of targeted antineoplastic drugs are discussed. Recently introduced mechanism-based systemic therapies for cancer may be more specific, less toxic, and more effective and represent a paradigm shift in treatment. Currently, receptor tyrosine kinases (RTKs), nonreceptor kinases, the angiogenic molecules, the enzymes involved in extracellular matrix degradation, and the enzymes responsible for protein anchorage to the cytoplasmic membrane are among the targets against which specific interventions have been developed. Monoclonal antibodies against the extracellular portion of RTKs and small-molecule inhibitors of their tyrosine kinase activity are strategies in more advanced phases of clinical development. Over the next few years, one can expect to see the results of many studies of such new pharmacologic agents or combinations. It seems likely, at this point, that targeted drugs will be used in association with existing medical, surgical, and radiotherapeutic modalities and will play an important role in the ultimate goal of reducing the burden of cancer. Targeting of molecular abnormalities that are differentially expressed in tumors may represent a more specific and less toxic way of treating cancer.