Anti-Angiogenic Drugs: Involvement in Cutaneous Side Effects and Wound-Healing Complication

Abstract

Significance: The uses of anti-angiogenic drugs have not only made an impact on the battle to eliminate cancer but are also responsible for a number of medical complications. The long-term use of these drugs has increased the spectrum and incidence of cutaneous side effects and wound-healing complications. It is, therefore, necessary to understand the overall impact that these drugs have on patient care. Recent Advances: This review highlights the role of vascular endothelial growth factor and fibroblast growth factor in angiogenesis and wound healing and looks at how angiogenic inhibitors promote wound-healing complications. Critical Issues: With an increased use of anti-angiogenic drugs for the treatment of various cancers and ocular diseases, there is an increased need for clinicians to define the risks and to optimize the usage of these drugs to reduce the incidence of cutaneous side effects and wound-healing complications. In addition, awareness is needed when treating patients on anti-angiogenic drugs so as not to exacerbate potential wound-healing complications when performing surgical procedures. Future Directions: Clinicians and surgeons will need to develop management guidelines to optimize patient care to reduce the risk of morbidity. When performing a surgical procedure, the impact of adverse effects from the use of anti-angiogenic drugs should be considered to ensure the welfare of the patient. In addition, the development of more specific inhibitors is necessary to reduce target effects to reduce the occurrence of adverse effects.

Richard J. Bodnar, PhD

Figure 1.

VEGF signaling pathways. VEGF activation of VEGFR sets into motion a complex network of intracellular signaling pathways that promote migration, proliferation, survival, and permeability. Activation of FAK and FYN promotes migration. Proliferation is through the activation of PLC-γ and GRB2-SOS. Production of nitric oxide (NO) and prostaglandins induces vascular permeability. Activation of AKT inhibits the apoptotic proteins Bad and caspase-3. AKT, protein kinase B; GRB2, growth factor receptor-bound protein 2; PLC-γ, phospholipase C-γ; SOS, son of sevenless; VEGF, vascular endothelial growth factor; VEGFR, VEGF receptor.

Figure 2.

FGF signaling pathways. FGF-1 or FGF-2 activation of FGFR promotes migration and proliferation of endothelial cells, fibroblasts, and epithelial cells. Migration is through the activation of PKC, and proliferation is promoted by the activation of Ras-MAPK pathways. FGF, fibroblast growth factor; FGFR, FGF receptor; MAPK, mitogen activated protein kinase; PKC, protein kinase C.