Cutaneous adverse effects of targeted therapies: Part II: Inhibitors of intracellular molecular signaling pathways

• Published in: Journal of the American Academy of Dermatology Vol. 72; no. 2; p. 221
• Main Authors: Macdonald, James B, Macdonald, Brooke, Golitz, Loren E, LoRusso, Patricia, Sekulic, Aleksandar
• Format: Journal Article
• Language: English
• Published: United States 01.02.2015
• Subjects: Alopecia - chemically induced; Antineoplastic Agents - adverse effects; Carcinoma, Squamous Cell - chemically induced; Drug Eruptions - diagnosis; Drug Eruptions - etiology; Drug Eruptions - therapy; Humans; Immunotherapy - adverse effects; Mitogen-Activated Protein Kinases - drug effects; Molecular Targeted Therapy - adverse effects; Panniculitis - chemically induced; Photosensitivity Disorders - chemically induced; Photosensitivity Disorders - therapy; Proto-Oncogene Proteins B-raf - antagonists & inhibitors; Proto-Oncogene Proteins c-akt - antagonists & inhibitors; Signal Transduction - drug effects; Skin Neoplasms - chemically induced; Skin Neoplasms - drug therapy; pruritus; keratoacanthoma; lambrolizumab; nivolumab; RAS; taste alteration; seborrheic dermatitis; PI3K-AKT-mTOR pathway; dysgeusia; trametinib; keratosis pilaris; everolimus; RAF inhibitors; dermatitis; immunotherapy; ipilimumab; autoimmune adverse effects; mTOR inhibitor; autoimmune dermopathies; B-RAF; dabrafenib; PI3 kinase inhibitor; verrucal keratosis; MEK inhibitors; vemurafenib; vitiligo; vismodegib; hair loss; PD-1 inhibitor; selumetinib; hedgehog signaling pathway; panniculitis; AKT inhibitor; loss of taste; temsirolimus; MAP kinase pathway; immune-related toxicities; keratotic squamoproliferative lesion; dual inhibitor; rapamycin; squamous cell carcinoma
• ISSN: 1097-6787
• DOI: 10.1016/j.jaad.2014.07.033

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.