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.

Source: Journal of Clinical Investigation