KRAS and colorectal carcinoma: However, two serious limitations persist due to the allele-specific nature of these inhibitors: (1) the G12C KRAS mutation accounts for only 3% of CRC patients [29], thereby severely limiting clinical utility, and (2) experimental studies have identified multiple resistance mechanisms to allele-specific KRAS inhibitors, including the emergence of new KRAS mutations (e.g., Y96C), KRAS amplification, unchecked activation of co-expressed WT RAS isozymes (e.g., via EGFR stimulation), mutations in NRAS, or acquired bypass mechanisms (MET amplification or new oncogenic fusions) [30,31,32,33,34].