Cutaneous adverse effects of targeted therapies: Part I: Inhibitors of the cellular membrane
James B Macdonald1, Brooke Macdonald2, Loren E Golitz3
1Department of Dermatology, Central Utah Clinic, Provo, Utah; Department of Pathology, Central Utah Clinic, Provo, Utah.
Abstract:
There has been a rapid emergence of numerous targeted agents in the oncology community in the last decade. This exciting paradigm shift in drug development lends promise for the future of individualized medicine. Given the pace of development and clinical deployment of targeted agents with novel mechanisms of action, dermatology providers may not be familiar with the full spectrum of associated skin-related toxicities. Cutaneous adverse effects are among the most frequently observed toxicities with many targeted agents, and their intensity can be dose-limiting or lead to therapy discontinuation. In light of the often life-saving nature of emerging oncotherapeutics, it is critical that dermatologists both understand the mechanisms and recognize clinical signs and symptoms of such toxicities in order to provide effective clinical management. Part I of this continuing medical education article will review in detail the potential skin-related adverse sequelae, the frequency of occurrence, and the implications associated with on- and off-target cutaneous toxicities of inhibitors acting at the cell membrane level, chiefly inhibitors of epidermal growth factor receptor, KIT, and BCR-ABL, angiogenesis, and multikinase inhibitors.
Insights
Targeted cancer therapies can cause skin toxicities. Dermatologists must recognize and manage these side effects for effective patient care.
Area of Science:
- Oncology
- Dermatology
- Pharmacology
Background:
- Targeted cancer therapies represent a significant advancement in individualized medicine.
- The rapid development of these agents outpaces dermatologists' familiarity with their cutaneous toxicities.
- Skin-related adverse effects are common and can impact treatment adherence.
Purpose of the Study:
- To review the spectrum of skin toxicities associated with targeted cancer agents.
- To enhance dermatologists' understanding of the mechanisms, clinical signs, and management of these toxicities.
- To focus on toxicities from inhibitors targeting cell membrane pathways.
Main Methods:
- Review of literature on targeted agents and their cutaneous side effects.
- Categorization of toxicities based on targeted pathways (e.g., EGFR, KIT, BCR-ABL, angiogenesis, multikinase inhibitors).
- Discussion of on- and off-target effects impacting the skin.
Main Results:
- Cutaneous adverse effects are frequent with targeted therapies.
- These toxicities can be dose-limiting or lead to treatment discontinuation.
- Understanding mechanisms is crucial for effective management.
Conclusions:
- Dermatologists require specialized knowledge to manage skin toxicities from novel oncotherapeutics.
- Early recognition and intervention are key to optimizing patient outcomes.
- This review provides a foundation for managing targeted agent-induced dermatologic conditions.
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