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Journal of the American Academy of Dermatology
Volume 72, n° 2
pages 221-236 (février 2015)
Doi : 10.1016/j.jaad.2014.07.033
accepted : 22 July 2014
Continuing Medical Education

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

James B. Macdonald, MD a, b, , Brooke Macdonald, BA c, Loren E. Golitz, MD d, e, Patricia LoRusso, DO f, Aleksandar Sekulic, MD, PhD g
a Department of Dermatology, Central Utah Clinic, Provo, Utah 
b Department of Pathology, Central Utah Clinic, Provo, Utah 
c Macdonald Graphic Design, Inc, Provo, Utah 
d Department of Dermatology, University of Colorado-Denver, Aurora, Colorado 
e Department of Pathology, University of Colorado-Denver, Aurora, Colorado 
f Department of Oncology, Wayne State University, Detroit, Michigan 
g Department of Dermatology, Mayo Clinic, Scottsdale, Arizona 

Correspondence to: James B. Macdonald, MD, Departments of Dermatology and Pathology, Central Utah Clinic, 1055 N 500 W, Ste 111, Provo, UT 84604.

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.

The full text of this article is available in PDF format.

Key words : AKT inhibitor, autoimmune adverse effects, autoimmune dermopathies, B-RAF, dabrafenib, dermatitis, dual inhibitor, dysgeusia, everolimus, hair loss, hedgehog signaling pathway, immunotherapy, immune-related toxicities, ipilimumab, keratoacanthoma, keratosis pilaris, keratotic squamoproliferative lesion, lambrolizumab, loss of taste, MAP kinase pathway, MEK inhibitors, mTOR inhibitor, nivolumab, panniculitis, PD-1 inhibitor, PI3K-AKT-mTOR pathway, PI3 kinase inhibitor, pruritus, RAF inhibitors, rapamycin, RAS, seborrheic dermatitis, selumetinib, squamous cell carcinoma, taste alteration, temsirolimus, trametinib, vemurafenib, vitiligo, verrucal keratosis, vismodegib

Abbreviations used : AE, CIA, CTLA-4, EGFR, HhSP, MAH, MAPK, MED, mTOR, PD-1, PTCH1, SCC, SMO, UVA

 Funding sources: None.
 Conflicts of interest: None declared.
 Date of release: February 2015
 Expiration date: February 2018

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