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These complexes can be recognised by antibodies and engineered into BiTEs, redirecting cytotoxic T-cell activity specifically against KRAS-G12C -mutant cancer cells.128 129 In addition, combining KRASi with metabolic pathway blockadesuch as targeting AGER-dependent macropinocytosis with RAGE229 or autophagy with chloroquinecan further enhance KRASi-induced cell death by increasing immunogenicity and activating damage-associated molecular pattern-mediated pathways (eg, high mobility group box 1-driven immunogenic cell death).106 110 Clinical translation of KRASiICB combinations has produced mixed outcomes

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Hoover, Kaili Liu, Trisha I