Cutaneous Toxicities of Small Molecules in Targeted Cancer Therapy Part I - Mechanisms of Toxicity.

Nykaza, Ian; Kwong, Bernice; Gordon, Allison · J Am Acad Dermatol · 2026

review · Level V

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Abstract

Advances in the understanding of cancer biology have led to a shift toward more precise, targeted anticancer therapies. Traditional chemotherapy acts as an intracellular poison to disrupt cell division or induce DNA damage resulting in cytotoxicity<sup>1</sup>. However, the effects of traditional chemotherapy are not relegated to neoplastic tissue, resulting in significant off-target cytotoxicity<sup>2</sup>. Targeted therapies were developed to provide a more specific approach to cancer treatment, focused on inhibiting the pathways involved in carcinogenesis and tumor growth. Small molecule inhibitors (SMIs) and antibody-based therapies are the two main pillars of this approach<sup>3</sup>. This review focuses on SMIs given their broad applicability across tumor types, rapidly expanding number of agents, and unique side effect profiles<sup>4,5</sup>. Part I of this continuing medical education article reviews mechanisms of toxicity of dermatologic adverse events associated with SMIs.