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.

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.