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.