Why Certain Anticancer Drugs Can Cause Heart Failure In Some Patients
Several types of cancer are characterized by overexpression of PDGFR proteins, and molecules that inhibit PDGFR signaling have proven useful anticancer therapeutics. Recently, however, several such anticancer drugs have been associated with clinical heart failure in some patients. Aarif Khakoo and colleagues, at the University of Texas MD Anderson Cancer Center, Houston, have now identified a role for PDGFR-beta in mouse heart muscle cells that might help explain why inhibitors of PDGFR signaling can cause heart failure.
In the study, expression and activation of PDGFR-beta was found to increase dramatically in the hearts of mice exposed to pressure overload (a model of high blood pressure). Further, mice lacking PDGFR-beta in heart muscle cells developed more severe heart failure when exposed to pressure overload than did normal mice. Further analysis indicated that PDGFR-beta in heart muscle cells contributes to the protective response to pressure overload by triggering the growth of new blood vessels, providing new insight into the physiologic functions of PDGFR-beta.
TITLE: Cardiomyocyte PDGFR-beta signaling is an essential component of the mouse cardiac response to load-induced stress http://www.jci.org/articles/view/39434?key=9ac310c34a9a682962db
AUTHOR: Aarif Y. Khakoo, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Source: Karen Honey
Journal of Clinical Investigation
Targeting Cancerous Vessels
By lowering the level of a neuronal protein, researchers halted the growth of blood vessels that tumors rely on for survival. The findings are reported online in the Journal of Experimental Medicine.
Formerly known for its effects on neuronal growth, the team found that the protein {delta}-catenin is also produced by cells in human blood vessels. By diminishing {delta}-catenin expression, the team disrupted vessel development, or angiogenesis, associated with inflammation in tumors and wounds. As expected, samples of human lung tumors expressed more {delta}-catenin than the surrounding tissues. And normal angiogenesis remained the same regardless of {delta}-catenin.
Because blocking {delta}-catenin stunts only inflammation-induced angiogenesis, the protein may be a promising anti-cancer target, says Charles Lin, an author on the study at Vanderbilt University Medical Center in Tennessee.