Concomitant Inhibition of FASN and SREBP Provides a Promising Therapy for CTCL

• DOI: 10.3390/cancers14184491
• Publication Date: 2022-09-19T02:12:43Z
• Authors: Cheng Chi; Lisa Harth; Marina Ramírez Ga...; Marina Passos Tor...; Chella Krishna Va...; Carsten Geisler; Charlotte Menné B...; Pia Rude Nielsen; Michael Bzorek; Jürgen C. Becker; Lise Mette Rahbek...; Niels Ødum; Anders Woetmann
• Keywords: Concomitant

Cutaneous T cell lymphoma (CTCL) is a group of non-Hodgkin’s primary cutaneous lymphomas, with Mycosis Fungoides and Sézary syndrome (SS) being the two most common subtypes. Fatty acid synthase (FASN) crucial enzyme that catalyses biosynthesis fatty acids, which has been reported to play an oncogenic role in various malignancies but not CTCL so far. Herein, we show FASN highly expressed lines peripheral blood mononuclear cells (PBMCs) from patients, while it PBMCs healthy individuals. The inhibition impairs viability, survival, proliferation, but, interestingly, also increases expression. However, inhibiting sterol regulatory element binding protein (SREBP), transcription factor promotes expression FASN, partially reversed upregulation induced by inhibitors. Thus, combination SREBP inhibitors enhanced effects on both SS where valid proliferation could be verified. Importantly, compared non-malignant cells, malignant are more sensitive SREBP, making promising novel therapeutic strategy CTCL.