KRAS Mutation/biomarker | Recent advances/diagnostic applications |
KRAS G12V [18] | Trametinib + Docetaxel (NSCLC), Cetuximab (CRC), Panitumumab (CRC) approved. Novel MEK, PI3K and AKT inhibitors in trials (e.g. cobimetinib, alpelisib, ipatasertib). KRAS G12V peptide vaccine in Phase 1 for NSCLC Diagnostic applications: Liquid biopsies detecting circulating tumor DNA (ctDNA) for monitoring response. ctDNA analysis provides early signal of clinical benefit or resistance. Biomarkers such as ctDNA, tMAF, mutation specific PD-L1 serve as hallmarks for cancer detection |
KRAS G13D [31] | Similar targeted drug approvals and trials as KRAS G12V based on MAP kinase pathway. Tumor mutant allele frequency (tMAF) tracks treatment effects. |
KRAS Q61H [34] | Rare mutation with MEK and AKT inhibition testing in preclinical models. Liquid biopsies offer insights into selective kinase inhibitor sensitivity. KRAS Q61H vaccine got 14% response rate leading to larger studies. |
KRAS G12C [18] | Chemosensitive mutation, standard treatment is chemotherapy. New MEK inhibitors (e.g. refametinib, trametinib) allow dual use with chemotherapy in trials. Co-blocking MEK and PI3K/AKT pathways under investigation. Mutation specific PD-L1 expression determines immunotherapy eligibility |
KRAS G12R [56] | Standard treatment based on limited data, newer agents needed. Increased genomic sequencing required to stratify patients for clinical trials. Advances include targeted approvals, molecular markers for selection/monitoring, liquid biopsies and clinical trials integrating genomics. |