TY - JOUR T1 - Pharmacokinetics, Clinical Indications, and Resistance Mechanisms in Molecular Targeted Therapies in Cancer JF - Pharmacological Reviews JO - Pharmacol Rev SP - 1351 LP - 1395 DO - 10.1124/pr.113.007807 VL - 65 IS - 4 AU - Benjamin Izar AU - Julia Rotow AU - Justin Gainor AU - Jeffrey Clark AU - Bruce Chabner A2 - Longo, Dan L. Y1 - 2013/10/01 UR - http://pharmrev.aspetjournals.org/content/65/4/1351.abstract N2 - The strategy for discovery and development of new cancer drugs has shifted the field from cytotoxic agents to therapies that selectively target oncogenic drivers. In the last decade, a number of targeted cancer therapies have been discovered and proven effective in a variety of hematological and solid malignancies. In this article, we review clinical pharmacokinetic characteristics of the U.S. Food and Drug Administration–approved targeted therapies and provide an overview of key clinical trials that led to approval of these drugs. The major limiting factor of targeted treatment is the development of resistance. We describe general principles of resistance and specific, clinically confirmed mechanisms of resistance to several therapies in different malignancies. ER -