The KIT and PDGFRA switch-control inhibitor DCC-2618 blocks growth and survival of multiple neoplastic cell types in advanced mastocytosis
oleh: Mathias Schneeweiss, Barbara Peter, Siham Bibi, Gregor Eisenwort, Dubravka Smiljkovic, Katharina Blatt, Mohamad Jawhar, Daniela Berger, Gabriele Stefanzl, Susanne Herndlhofer, Georg Greiner, Gregor Hoermann, Emir Hadzijusufovic, Karoline V. Gleixner, Peter Bettelheim, Klaus Geissler, Wolfgang R. Sperr, Andreas Reiter, Michel Arock, Peter Valent
| Format: | Article |
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| Diterbitkan: | Ferrata Storti Foundation 2018-05-01 |
Deskripsi
Systemic mastocytosis is a complex disease defined by abnormal growth and accumulation of neoplastic mast cells in various organs. Most patients exhibit a D816V-mutated variant of KIT, which confers resistance against imatinib. Clinical problems in systemic mastocytosis arise from mediator-related symptoms and/or organ destruction caused by malignant expansion of neoplastic mast cells and/or other myeloid cells in various organ systems. DCC-2618 is a spectrum-selective pan KIT and PDGFRA inhibitor which blocks KIT D816V and multiple other kinase targets relevant to systemic mastocytosis. We found that DCC-2618 inhibits the proliferation and survival of various human mast cell lines (HMC-1, ROSA, MCPV-1) as well as primary neoplastic mast cells obtained from patients with advanced systemic mastocytosis (IC50