The Current Status of Medicine Development for Precision Therapy and Diagnosis Targeting KRAS^G12C

Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations represent one of the most frequent oncogenic alterations in human cancers. Notably, the glycine-to-cysteine substitution at codon 12 (G12C) results in constitutive activation of the KRAS protein, which promotes tumor initiation and progression. In recent years, small-molecule inhibitors targeting KRAS^G12C have been well developed and approved by the US Food and Drug Administration (FDA) for clinical use, leading to improved therapeutic outcomes for relevant cancers. However, there is still a lack of effective non-invasive diagnostic tools to evaluate the status of KRAS^G12C. Molecular imaging, especially positron emission tomography (PET), a non-invasive functional imaging modality, has considerable potential for precision diagnosis and treatment as well as drug development. This review systematically outlined the biological features of the KRAS^G12C protein, highlighted recent advances in the development of KRAS^G12C-related inhibitors, and discussed the current progress in designing probes for imaging this mutation. The review also proposes specific criteria for the development of ¹⁸F-labeled PET tracers targeting KRAS^G12C.