The current status of medicine development for precision therapy and diagnosis targeting KRASG12C

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 KRASG12C 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 KRASG12C. 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 KRASG12C protein, highlighted recent advances in the development of KRASG12C-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 KRASG12C.