While ongoing studies are leveraging tumor cell-expression of B7-H3 for therapeutic intervention (CAR-T therapy, anti-B7-H3-ADCs, anti-B7-H3 radiotheranostics)46–50, we propose an additional approach focused on disrupting 4Ig-B7-H3 dimerization to inhibit tumor growth and new therapeutic agents that accomplish this might prove effective in the control of B7-H3-driven tumor progression and resistance. The gene discussed is CD276; the disease is neoplasm.