Current oncology reports
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Current oncology reports · May 2019
ReviewSystemic Histiocytosis (Langerhans Cell Histiocytosis, Erdheim-Chester Disease, Destombes-Rosai-Dorfman Disease): from Oncogenic Mutations to Inflammatory Disorders.
Provide an overview of recent progress in decoding the pathogenesis and treatment of systemic histiocytoses. ⋯ Advances in molecular techniques over the last few years, enabling the identification of several MAPK mutations in lesion histiocytes, have revolutionized our understanding of histiocytosis that led to a revised classification and new treatments. Since the 2010 discovery of the BRAFV600E mutation in 57% of Langerhans cell histiocytosis (LCH) lesions, several other kinase mutations have been found, mostly in the MAPK pathway, and also in other key signaling pathways, in LCH, Erdheim-Chester Disease (ECD) and, less frequently, Destombes-Rosai-Dorfman disease (RDD). Those revolutionary breakthroughs enhanced our understanding of the pathogenesis of histiocytosis and led to trials with targeted therapies that demonstrated notable efficacy.
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Current oncology reports · May 2019
ReviewTargeted Therapies for the Treatment of Glioblastoma in Adults.
Targeted therapies are part of biomarker-driven strategies that exploit actionable molecular targets and have gained traction following survival benefits demonstrated in various systemic malignancies. In glioblastoma, where therapeutic options remain scarce and prognosis poor, targeted therapies offer an attractive treatment alternative and are actively examined in clinical trials. In this review, we summarize the targeted therapies, including traditional small molecule inhibitors and monoclonal antibodies as well as immunotherapeutic approaches that are examined in clinical trials, and discuss the challenges of using them for the treatment of glioblastoma. ⋯ Despite initial speculations, phase II/III trials of targeted therapies in adult patients with glioblastoma have largely failed. Recent trials have focused on improving patient stratification, drug-tissue penetration, and target and compensatory pathway inhibition to optimize treatment response. In contrast to traditional small molecule and monoclonal antibody therapies, cancer immunotherapy may target specific molecular or immune checkpoint target(s) to trigger immune responses against glioblastoma. Early phase clinical trials of immunotherapy have shown encouraging results, and larger randomized trials are ongoing. Targeted therapies are being actively studied in clinical trials. Patients with glioblastoma should be prioritized for clinical trial participation.