title: Cutaneous adverse effects of targeted therapies: Part II: Inhibitors of intracellular molecular signaling pathways.
abstract: The last decade has spawned an exciting new era of oncotherapy in dermatology, including the development of targeted therapies for metastatic melanoma and basal cell carcinoma. Along with skin cancer, deregulation of the PI3K-AKT-mTOR and RAS-RAF-MEK-ERK intracellular signaling pathways contributes to tumorigenesis of a multitude of other cancers, and inhibitors of these pathways are being actively studied. Similar to other classes of targeted therapies, cutaneous adverse effects are among the most frequent toxicities observed with mitogen-activated protein kinase pathway inhibitors, PI3K-AKT-mTOR inhibitors, hedgehog signaling pathway inhibitors, and immunotherapies. Given the rapid expansion of these families of targeted treatments, dermatologists will be essential in offering dermatologic supportive care measures to cancer patients being treated with these agents. Part II of this continuing medical education article reviews skin-related adverse sequelae, including the frequency of occurrence and the implications associated with on- and off-target cutaneous toxicities of inhibitors of the RAS-RAF-MEK-ERK pathway, PI3K-AKT-mTOR pathway, hedgehog signaling pathway, and immunotherapies.
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; D000970:Antineoplastic Agents / Q000009:adverse effects*; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced; D003875:Drug Eruptions / Q000175:diagnosis / Q000209:etiology* / Q000628:therapy; D006801:Humans; D007167:Immunotherapy / Q000009:adverse effects; D020928:Mitogen-Activated Protein Kinases / Q000187:drug effects; D058990:Molecular Targeted Therapy / Q000009:adverse effects*; D015434:Panniculitis / Q000139:chemically induced; D010787:Photosensitivity Disorders / Q000139:chemically induced / Q000628:therapy; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors; D015398:Signal Transduction / Q000187:drug effects*; D012878:Skin Neoplasms / Q000139:chemically induced / Q000188:drug therapy
chemical_list: D000970:Antineoplastic Agents; D048493:Proto-Oncogene Proteins B-raf; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases
keywords: AKT inhibitor; B-RAF; MAP kinase pathway; MEK inhibitors; PD-1 inhibitor; PI3 kinase inhibitor; PI3K-AKT-mTOR pathway; RAF inhibitors; RAS; autoimmune adverse effects; autoimmune dermopathies; dabrafenib; dermatitis; dual inhibitor; dysgeusia; everolimus; hair loss; hedgehog signaling pathway; immune-related toxicities; immunotherapy; ipilimumab; keratoacanthoma; keratosis pilaris; keratotic squamoproliferative lesion; lambrolizumab; loss of taste; mTOR inhibitor; nivolumab; panniculitis; pruritus; rapamycin; seborrheic dermatitis; selumetinib; squamous cell carcinoma; taste alteration; temsirolimus; trametinib; vemurafenib; verrucal keratosis; vismodegib; vitiligo