Fig. 7: Paxalisib and mirdametinib drive synergistic growth inhibition in a subset of pHGG cell lines.

The BRAID model presents synergistic effects of paxalisib (pax) and mirdametinib (mir) following a 7-day treatment in 7-cell lines: H3.3 K27M DIPGs; SJ-DIPGX37c, SJ-DIPGX29c, SJ-DIPGX7c, H3.3 G34R pHGGs; SJ-HGGX42c, SJ-HGGX6c, and astrocyte controls HABS and iAstro. The parameter κ measures the type of interaction: κ < 0 implies antagonism, κ = 0 implies additivity, and κ > 0 implies synergy). The index of achievable efficacy (IAE) quantifies the degree to which the drug combination achieves a minimal level of efficacy within a defined concentration range. Higher IAE means the combination was more efficacious. In this experiment, it was defined as a 50% reduction of cell viability (black line) at concentrations ≤ 1 μM (dotted lines). The 90% reduction of viability isobole (white line) is included for reference.