Technical Articles

On the battlefield of cancer treatment, KRAS gene mutations have long been a "tough adversary." Frequently implicated in pancreatic cancer, colorectal cancer, and non-small cell lung cancer (NSCLC), these mutations enable tumor cells to grow uncontrollably. However, the lack of binding pockets on the KRAS protein surface made it resistant to traditional drugs, once rendering it an "undruggable" target. In recent years, the emergence of KRAS G12C inhibitors has broken this impasse. The approvals of sotorasib and adagrasib have brought new hope to patients with advanced NSCLC. These drugs lock the KRAS G12C mutant in an inactive state by binding to its cysteine residue, thereby inhibiting downstream signaling pathways. Clinical trial results have been encouraging, demonstrating high objective response rates (ORRs) and disease control rates (DCRs).