Role of STAT3 in Cutaneous Side Effects Induced by Multi-targeted Tyrosine Kinase Inhibitors

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  • マルチキナーゼ阻害薬による皮膚障害におけるSTAT3の役割

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Abstract

<p>A large number of molecular-targeted drugs have been discovered, and we are facing diverse adverse effects that we have not experienced previously. In particular, dermatological toxicity is frequently caused by various molecular-targeted drugs, and this side effect often contributes to the interruption of therapy and decreases the quality of life (QOL) in patients. Especially, typical dermatitis induced by multi-targeted tyrosine kinase inhibitors (mTKI), hand-foot skin reaction (HFSR), is a serious adverse reaction that affects the therapeutic outcomes of mTKI, although pathological and molecular mechanisms of this reaction are unclear. This review summarizes our findings about the roles of the signal transducer and activator of transcription 3 (STAT3) in the mechanisms of mTKI-induced dermatitis, risk factors of HFSR, and mechanism-based prophylaxis of HFSR:</p><p>1) Molecular biological roles of STAT3 in the mTKI-induced keratinocyte toxicity</p><p>2) Association between mTKI-induced HFSR and STAT3 polymorphisms</p><p>3) A novel prophylaxis strategy based on maintaining STAT3 activity</p><p>These findings provide important perceptions on the mechanisms of HFSR and the identification of predictive factors for toxicity of mTKI, and it may lead to the realization of precision medicine in molecular-targeted therapy.</p>

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