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KRASG12D in Cancer: Structural Insights, Signaling Pathways, and Progress in Targeted Inhibitor Design

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Targeting KRASG12D has gained traction due to potential breakthroughs in effective inhibitors.
The non-covalent inhibitor MRTX1133 demonstrated significant anti-tumor activity via the Switch II pocket.
Innovative therapeutic approaches such as PROTAC-based degraders are explored to counteract drug resistance.
Challenges like selectivity and adaptive resistance continue to impede the development of KRASG12D-targeted therapies.

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Review highlights KRASG12D's role in pancreatic, colorectal, and lung cancers, indicating advances in targeted inhibitors.

Zhou et al. (2025) studied this question.

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