Journal: Clinical Cancer Research

Article Title: MEK Inhibition Synergizes with TYK2 Inhibitors in NF1-Associated Malignant Peripheral Nerve Sheath Tumors

doi: 10.1158/1078-0432.CCR-22-3722

Figure Lengend Snippet: The specific TYK2 inhibitor deucravacitinib (BMS-986165) decreases MPNST cell proliferation at lower doses. The MPNST cell lines JW23.3 ( A and B ), JH-2–002 ( C and D ), and MPNST-724 ( E and F ) were treated with the indicated doses of the specific TYK2 inhibitor deucravacitinib or the pan-JAK inhibitor baricitinib for 3 days in IncuCyte live cell proliferation assays.

Article Snippet: Mice were randomized into four groups and given 30 mg/kg deucravacitinib (MedChemExpress, in 5% ethanol/5% TPGS/90% PEG300) and/or 1.5 mg/kg mirdametinib (SpringWorks Therapeutics, in 0.5% HPMC/0.2% Tween-80/water), or vehicle control daily via oral gavage for 3 to 4 weeks.

Techniques:

Journal: Clinical Cancer Research

Article Title: MEK Inhibition Synergizes with TYK2 Inhibitors in NF1-Associated Malignant Peripheral Nerve Sheath Tumors

doi: 10.1158/1078-0432.CCR-22-3722

Figure Lengend Snippet: Inhibitors of TYK2 (deucravacitinib) and MEK (mirdametinib) act synergistically to reduce proliferation and increase apoptosis in JW23.3 MPNST cells. Cell confluence and apoptosis were analyzed by the IncuCyte assay after 48-hour incubation with drugs. Synergy was analyzed using Synergy Finder software by the HSA method for ( A ) inhibition of cell proliferation or ( B ) apoptosis, and mean synergy score is reported ( P < 0.05 vs. drug alone). Intensity of red color indicates synergy score for each dose combination, whereas green indicates antagonism. C, Representative images of JW23.3 cells treated for 48 hours. YOYO-1 green fluorescence indicates apoptotic cells.

Article Snippet: Mice were randomized into four groups and given 30 mg/kg deucravacitinib (MedChemExpress, in 5% ethanol/5% TPGS/90% PEG300) and/or 1.5 mg/kg mirdametinib (SpringWorks Therapeutics, in 0.5% HPMC/0.2% Tween-80/water), or vehicle control daily via oral gavage for 3 to 4 weeks.

Techniques: Incubation, Software, Inhibition, Fluorescence

Journal: Clinical Cancer Research

Article Title: MEK Inhibition Synergizes with TYK2 Inhibitors in NF1-Associated Malignant Peripheral Nerve Sheath Tumors

doi: 10.1158/1078-0432.CCR-22-3722

Figure Lengend Snippet: The combination of drugs inhibiting TYK2 and MEK block MPNST tumor growth in mice. A, Schematic diagram of treatment paradigm. Mice with JW23.3 MPNST xenograft tumors ( n = 6 per group; B ), WU-386 MPNST PDX tumors ( n = 3 per group; C ), or JH-2–002 MPNST xenograft tumors ( n = 5 per group; D ) were treated daily with 1.5 mg/kg mirdametinib (Mirda), 30 mg/kg deucravacitinib (Deucra, BMS-986165), the combination of drugs, or vehicle control for 3 weeks or until tumors reached the maximum allowed volume. *, P < 0.05 vs. vehicle control; a , P < 0.05 for drug combination vs. drugs alone. E and F, Diagram of TYK2/STAT3 and MEK/ERK pathways after treatment with Deucra and/or Mirda in MPNST cells. (Illustrations were created with BioRender.com .)

Article Snippet: Mice were randomized into four groups and given 30 mg/kg deucravacitinib (MedChemExpress, in 5% ethanol/5% TPGS/90% PEG300) and/or 1.5 mg/kg mirdametinib (SpringWorks Therapeutics, in 0.5% HPMC/0.2% Tween-80/water), or vehicle control daily via oral gavage for 3 to 4 weeks.

Techniques: Blocking Assay, Control