Treatment of Langerhans Cell Histiocytosis and Histiocytic Disorders: A Focus on MAPK Pathway Inhibitors

Geerlinks, Ashley V.; Abla, Oussama

doi:10.1007/s40272-023-00569-8

Cited by 5 publications

(2 citation statements)

References 81 publications

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“…Cobimetinib's allosteric inhibition of MEK1/2 reduces ERK1/2 phosphorylation [18]. Apart from vemurafenib and cobimetinib, other small molecules targeting the RAS/MAPK pathway, such as dabrafenib, trametinib, encorafenib, and sorafenib, have been employed, alone or in combination with other drugs, in a small number of patients with L-group histiocytosis [19][20][21] (Figure 4). For patients without druggable mutations or those refractory to kinase inhibitors, treatment options include interferon-α, cladribine, IL-1 inhibitors, glucocorticoids, or chemotherapy [5,22].…”

Section: Discussionmentioning

confidence: 99%

Erdheim–Chester Disease Due to a Novel Internal Duplication of NRAS: Response to Targeted Therapy with Cobimetinib

Riancho,

Hernández,

González-Vela

et al. 2023

IJMS

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Histiocytoses encompass a group of exceptionally rare disorders characterized by the abnormal infiltration of tissues by histocytes. Among these, Erdheim–Chester disease (ECD) stands out as a multisystem histiocytosis that typically affects bones and various other tissues. Historically, the treatment of ECD has been challenging. However, recent breakthroughs in our understanding, particularly the discovery of somatic mutations in the RAS-MAPK pathway, have opened new opportunities for targeted therapy in a significant subset of patients with ECD and other histiocytoses. In this report, we present the case of a patient with ECD harboring a previously unidentified microduplication in the NRAS gene in a small fraction of skin cells. This discovery played a pivotal role in tailoring an effective therapeutic approach involving kinase inhibitors downstream of NRAS. This case underscores the crucial role of deep sequencing of tissue samples in ECD, enabling the delivery of personalized targeted therapy to patients.

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Section: Discussionmentioning

confidence: 99%

Erdheim–Chester Disease Due to a Novel Internal Duplication of NRAS: Response to Targeted Therapy with Cobimetinib

Riancho,

Hernández,

González-Vela

et al. 2023

IJMS

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“…The discovery of recurrent activating mutations and translocations highlights the potential for targeted inhibition in subsets of patients with JXG bearing these alterations, especially in refractory diseases. 21 Zhang et al 11 reported a patient with SJXG who received a trial of anti-BRAF targeted therapy (dabrafenib) and showed significant regression of both ocular and systemic lesions. Another child with an aggressive and refractory BRAFV600E-positive multifocal CNS-JXG responded dramatically to dabrafenib.…”

Section: The Treatment Modalities In Sjxgmentioning

confidence: 99%

Frequent detection of genetic aberrations reveals novel pathogenesis and treatment modalities in systemic juvenile xanthogranuloma

Xu,

Ma,

Yao

et al. 2023

Pediatric Investigation

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Frequent detection of genetic aberrations reveals novel pathogenesis and treatment modalities in systemic juvenile xanthogranulomaJuvenile xanthogranuloma (JXG), the most common form of non-Langerhans cell histiocytosis (non-LCH), is generally confined to the skin during infancy and early childhood. 1 JXG rarely involves extracutaneous tissues or systemic organs, resulting in high morbidity and mortality rates. Clonality in JXG has been verified by histopathological and genetic analyses, which have shown it to be tumorous rather than a reactive disorder of JXG. 2 However, the exact etiopathogenesis of JXG remains unclear.Diverse organs and systems can be involved in systemic JXG (SJXG). The most common extracutaneous sites include the eyes, central nervous system (CNS), liver, and lungs. Compared with cutaneous JXG, SJXG usually requires more aggressive treatment. Conventionally, the first-line treatment for SJXG is based on chemotherapy used in Langerhans cell histiocytosis (LCH), such as corticosteroids and vinblastine, with various responses. 3 Alternative regimens include methotrexate, cladribine, and cytarabine when initial chemotherapy fails.In the past decade, genomic studies have been conducted on histiocytosis, including JXG, and distinctive genetic abnormalities have been discovered (e.g., BRAFV600E mutations and ALK translocations). 4,5 These novel genetic discoveries further confirmed the tumorigenesis of JXG and highlighted the possibility of therapeutic targets in refractory or severe cases. GENETIC ABERRATIONS IN THE PATHOGENESIS OF SJXGJXG is involved in the clonal proliferation of histiocytes by human androgen receptor assay (HUMARA). 2 However, the drivers of cell proliferation in JXG remain to be elucidated. Several cases of JXG have been reported

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A rare case of primary central nervous system histiocytic sarcoma harboring a novel ARHGAP45::BRAF fusion: a case report and literature review

Zhang,

Zheng

et al. 2023

Brain Tumor Pathol

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Treatment of Langerhans Cell Histiocytosis and Histiocytic Disorders: A Focus on MAPK Pathway Inhibitors

Cited by 5 publications

References 81 publications

Erdheim–Chester Disease Due to a Novel Internal Duplication of NRAS: Response to Targeted Therapy with Cobimetinib

Erdheim–Chester Disease Due to a Novel Internal Duplication of NRAS: Response to Targeted Therapy with Cobimetinib

Frequent detection of genetic aberrations reveals novel pathogenesis and treatment modalities in systemic juvenile xanthogranuloma

A rare case of primary central nervous system histiocytic sarcoma harboring a novel ARHGAP45::BRAF fusion: a case report and literature review

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