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Current State of Targeted Therapy in Adult Langerhans Cell Histiocytosis and Erdheim–Chester Disease

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Abstract

The mitogen-activated protein kinase (MAPK) pathway is a key driver in many histiocytic disorders, including Langerhans cell histiocytosis (LCH) and Erdheim–Chester disease (ECD). This has led to successful and promising treatment with targeted therapies, including BRAF inhibitors and MEK inhibitors. Additional novel inhibitors have also demonstrated encouraging results. Nevertheless, there are several problems concerning targeted therapy that need to be addressed. These include, among others, incomplete responsiveness and the emergence of resistance to BRAF inhibition as observed in other BRAF-mutant malignancies. Drug resistance and relapse after treatment interruption remain problems with current targeted therapies. Targeted therapy does not seem to eradicate the mutated clone, leading to inevitable relapes, which is a huge challenge for the future. More fundamental research and clinical trials are needed to address these issues and to develop improved targeted therapies that can overcome resistance and achieve long-lasting remissions.

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Authors and Affiliations

  1. Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

    He Lin & Xin-xin Cao

  2. State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Beijing, China

    He Lin & Xin-xin Cao

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This study was supported by grants from institutional research funding provided by the Beijing Natural Science Haidian frontier Foundation (Grant no. L222081 to Cao XX) and the National High Level Hospital Clinical Research Funding (2022-PUMCH-A-193).

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He Lin, Xin-xin Cao declare that they have no conflicts of interest that might be relevant to the contents of this manuscript.

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H.L. and X.C. wrote the main manuscript text. H.L. prepared figures and tables. X.C. reviewed the manuscript and provided helpful comments. All authors read and approved the final manuscript.

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Lin, H., Cao, Xx. Current State of Targeted Therapy in Adult Langerhans Cell Histiocytosis and Erdheim–Chester Disease. Targ Oncol 19, 691–703 (2024). https://doi.org/10.1007/s11523-024-01080-x

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