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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