Molecular mechanisms for vascular complications of targeted cancer therapies.
Molecularly targeted anti-cancer therapies have revolutionized cancer treatment by improving both quality of life and survival in cancer patients. However, many of these drugs are associated with cardiovascular toxicities that are sometimes dose-limiting. Moreover, the long-term cardiovascular consequences of these drugs, some of which are used chronically, are not yet known. Although the scope and mechanisms of the cardiac toxicities are better defined, the mechanisms for vascular toxicities are only beginning to be elucidated. This review summarizes what is known about the vascular adverse events associated with three classes of novel anti-cancer therapies: vascular endothelial growth factor (VEGF) inhibitors, breakpoint cluster-Abelson (BCR-ABL) kinase inhibitors used to treat chronic myelogenous leukaemia (CML) and immunomodulatory agents (IMiDs) used in myeloma therapeutics. Three of the best described vascular toxicities are reviewed including hypertension, increased risk of acute cardiovascular ischaemic events and arteriovenous thrombosis. The available data regarding the mechanism by which each therapy causes vascular complication are summarized. When data are limited, potential mechanisms are inferred from the known effects of inhibiting each target on vascular cell function and disease. Enhanced understanding of the molecular mechanisms of vascular side effects of targeted cancer therapy is necessary to effectively manage cancer patients and to design safer targeted cancer therapies for the future.
Department of Medicine, Division of Hematology/Oncology, Tufts Medical Center, Boston, MA 02111, U.S.A. Molecular Cardiology Research Institute, Tufts Medical Center, Boston, MA 02111, U.S.A. srilagopal@gmail.com ijaffe@tuftsmedicalcenter.org.
Srila
S
Gopal
Department of Medicine, Division of Hematology/Oncology, Tufts Medical Center, Boston, MA 02111, U.S.A.
Kenneth B
KB
Miller
Molecular Cardiology Research Institute, Tufts Medical Center, Boston, MA 02111, U.S.A. Department of Medicine, Division of Cardiology, Tufts Medical Center, Boston, MA 02111, U.S.A. srilagopal@gmail.com ijaffe@tuftsmedicalcenter.org.
Iris Z
IZ
Jaffe
D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D002318:Cardiovascular Diseases / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D058990:Molecular Targeted Therapy / Q000009:adverse effects*; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism
D000970:Antineoplastic Agents
VEGF inhibitors; targeted cancer therapy; tyrosine kinase inhibitors; vascular disease