Skin Toxicity of Targeted Cancer Agents: Mechanisms and Intervention

Abstract

In recent years, targeted agents have rapidly evolved as effective tools in the clinical management of a broad range of malignant diseases. These agents disrupt molecular mechanisms and signaling modules that drive the malignant phenotype in defined subsets of malignancies. Beyond the intended cellular targets crucial to tumor growth and progression, these agents also affect signal transduction in normal cells and tissues. The resulting adverse events and their clinical management continue to change, as newer agents with an ever-increasing target spectrum are developed. We provide a succinct overview of dermatologic toxicities arising from the targeting of receptor tyrosine kinases and downstream effectors. Emergent insights into the pathomechanisms involved and the use of this knowledge base to alleviate cutaneous adverse events are discussed.

Avasimibe Encapsulated in Human Serum Albumin Blocks Cholesterol Esterification for Selective Cancer Treatment

“…57–60 Targeting oncogenic protein kinase signaling pathways has reduced the off-targeting effect and non-specific toxicity. 61, 62 In spite of the benefits, the complicated therapeutic mechanism 63, 64 and the new adverse effects 65, 66 of targeted agents limit the clinical outcomes for cancer patients. 67, 68 …”

Epidermal RAF prevents allergic skin disease

“…Many inhibitory compounds have been developed that are currently in clinical trials or have reached the clinic. Reflecting the function of the pathway in skin, cutaneous toxicities are one of the main adverse effects of these therapies; they can be severe and lead to an interruption of the therapy or to its termination ( Belum et al, 2013 ; Curry et al, 2014 ; Dy and Adjei, 2013 ). These adverse effects can be roughly classified as inflammatory reactions, elicited chiefly by blocking EGFR or MEK; and proliferative events, caused by multikinase inhibitors such as sorafenib or by more specific RAF inhibitors (vemurafenib, dabrafenib).…”

Pharmacovigilance in oncology: evaluation of current practice and future perspectives

“…Initially acclaimed as almost free from severe side effects, all these targeted agents have a toxicity profile that could influence patient care, QoL and compliance to therapy. Dermatological and neurological toxicity are without a doubt among the most common side effects of these new agents [41,42].…”