Figure 6 from DIPG Harbors Alterations Targetable by MEK Inhibitors, with Acquired Resistance Mechanisms Overcome by Combinatorial Inhibition

Abstract

<p>Synergy of combined dasatinib and trametinib in BRAF<sup>G469V</sup>-driven DIPG cells. <b>A,</b> Cell viability matrices for ICR-B169 parental (gray) and trametinib-resistant clones T1 (<i>MEK2</i><sup>I115N</sup>, pink), (T3 <i>MEK1</i><sup>I141S</sup>, purple), and T6 (<i>MEK1</i><sup>K57N</sup>, red), treated with distinct combinations of dasatinib (<i>y</i>-axes) and trametinib (<i>x</i>-axes) ranging from 0 to 10 μmol/L. A heat map is overlaid to the proportions of viable cells remaining, colored according to the key provided from 1.0 (black, all cells) to 0 (red, no viable cells). <b>B,</b> Excess above BLISS matrices for ICR-B169 parental and trametinib-resistant clones treated with distinct combinations of dasatinib (<i>y</i>-axes) and trametinib (<i>x</i>-axes) ranging from 0 to 10 μmol/L. A heat map is overlaid to the excess score, colored according to the key provided from 0.4 (red, enhanced effects) to 0 (green, no difference). <b>C,</b> BLISS synergy maps for ICR-B169 parental and trametinib-resistant clones treated with distinct combinations of dasatinib (<i>y</i>-axes) and trametinib (<i>x</i>-axes) ranging from 0 to 10 μmol/L. The heat map represents the δ score colored according to the key provided from 30 (red, high degree of synergy) to −30 (green, antagonism).</p>

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