title: Cutaneous adverse effects of targeted therapies: Part I: Inhibitors of the cellular membrane.
abstract: There has been a rapid emergence of numerous targeted agents in the oncology community in the last decade. This exciting paradigm shift in drug development lends promise for the future of individualized medicine. Given the pace of development and clinical deployment of targeted agents with novel mechanisms of action, dermatology providers may not be familiar with the full spectrum of associated skin-related toxicities. Cutaneous adverse effects are among the most frequently observed toxicities with many targeted agents, and their intensity can be dose-limiting or lead to therapy discontinuation. In light of the often life-saving nature of emerging oncotherapeutics, it is critical that dermatologists both understand the mechanisms and recognize clinical signs and symptoms of such toxicities in order to provide effective clinical management. Part I of this continuing medical education article will review in detail the potential skin-related adverse sequelae, the frequency of occurrence, and the implications associated with on- and off-target cutaneous toxicities of inhibitors acting at the cell membrane level, chiefly inhibitors of epidermal growth factor receptor, KIT, and BCR-ABL, angiogenesis, and multikinase inhibitors.
authors.affiliation: Department of Dermatology, Central Utah Clinic, Provo, Utah; Department of Pathology, Central Utah Clinic, Provo, Utah. Electronic address: macdonjb@gmail.com.
authors.forename: James B
authors.initials: JB
authors.lastname: Macdonald
authors.affiliation: Macdonald Graphic Design, Inc, Provo, Utah.
authors.forename: Brooke
authors.initials: B
authors.lastname: Macdonald
authors.affiliation: Department of Dermatology, University of Colorado-Denver, Aurora, Colorado; Department of Pathology, University of Colorado-Denver, Aurora, Colorado.
authors.forename: Loren E
authors.initials: LE
authors.lastname: Golitz
authors.affiliation: Department of Oncology, Wayne State University, Detroit, Michigan.
authors.forename: Patricia
authors.initials: P
authors.lastname: LoRusso
authors.affiliation: Department of Dermatology, Mayo Clinic, Scottsdale, Arizona.
authors.forename: Aleksandar
authors.initials: A
authors.lastname: Sekulic
mesh_terms: D000505:Alopecia / Q000139:chemically induced; D020533:Angiogenesis Inhibitors / Q000009:adverse effects; D000970:Antineoplastic Agents / Q000009:adverse effects*; D002462:Cell Membrane / Q000187:drug effects*; D017454:Dermatitis, Photoallergic / Q000209:etiology; D004305:Dose-Response Relationship, Drug; D003875:Drug Eruptions / Q000175:diagnosis* / Q000209:etiology* / Q000628:therapy; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D016044:Fusion Proteins, bcr-abl / Q000037:antagonists & inhibitors; D006201:Hair Diseases / Q000139:chemically induced*; D006801:Humans; D058990:Molecular Targeted Therapy / Q000009:adverse effects*; D052016:Mucositis / Q000139:chemically induced; D009260:Nail Diseases / Q000139:chemically induced
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D066246:ErbB Receptors; D016044:Fusion Proteins, bcr-abl
keywords: BCR-ABL; HER2; KIT; adverse sequelae; alopecia; antiangiogenic agents; anticancer; bevacizumab; cancer treatment; canertinib; cetuximab; chemotherapy; cutaneous adverse effects; dasatinib; dermatologic toxicities; disturbed wound healing; drug eruption; drug rash; drug reaction; dry skin; dual kinase inhibitors; epidermal growth factor receptor inhibitors; erbB receptor; erlotinib; gefitinib; genital rash; hyperkeratotic hand–foot skin reaction; imatinib; lapatinib; macular eruption; monoclonal antibodies; morbilliform; mucocutaneous hemorrhage; mucositis; multikinase inhibitors; nilotinib; panitumumab; papulopustular eruption; paronychia; pazopanib; photosensitivity; pigment changes; platelet-derived growth factor receptor; ranibizumab; side effects; small molecule; sorafenib; stomatitis; sunitinib; supportive oncodermatology; targeted therapy; toxic erythema; tyrosine kinase inhibitors; vandetanib; vascular endothelial growth factor; xerosis