RT Journal Article
SR Electronic
T1 Pharmacokinetics, Clinical Indications, and Resistance Mechanisms in Molecular Targeted Therapies in Cancer
JF Pharmacological Reviews
JO Pharmacol Rev
FD American Society for Pharmacology and Experimental Therapeutics
SP 1351
OP 1395
DO 10.1124/pr.113.007807
VO 65
IS 4
A1 Benjamin Izar
A1 Julia Rotow
A1 Justin Gainor
A1 Jeffrey Clark
A1 Bruce Chabner
A2 Dan L. Longo
YR 2013
UL http://pharmrev.aspetjournals.org/content/65/4/1351.abstract
AB 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.