Cutaneous side effects of inhibition of VEGF signal transduction

Abstract

The VEGF signaling pathway (including ligands, surface-bound receptors and intracellular downstream signaling cascades) is critically involved in angiogenesis under normal and pathological conditions, in particular in malignant tumors. As a consequence, several therapies that target specific components of this pathway have been approved for clinical use or are in various stages of clinical development. Currently, the monoclonal antibodies bevacizumab and ranibizumab, as well as the small-molecule kinase inhibitors sorafenib and sunitinib, have been approved for cancer therapy. The spectrum of cutaneous side effects elicited by bevacizumab is considerably less pronounced than that seen with EGF inhibitors and includes peripheral sensory neuropathy, stomatitis, skin dryness, skin discoloration and exfoliative dermatitis. In contrast, unwanted cutaneous side effects seen with the less specific small molecule compounds include pruritic exanthems, nail changes, cheilitis and the painful hand-foot-syndrome.