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

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 cytotoxicity1. However, the effects of traditional chemotherapy are not relegated to neoplastic tissue, resulting in significant off-target cytotoxicity2. 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 approach3. This review focuses on SMIs given their broad applicability across tumor types, rapidly expanding number of agents, and unique side effect profiles4,5. Part I of this continuing medical education article reviews mechanisms of toxicity of dermatologic adverse events associated with SMIs.