KRAS Mutation — Key Genetic Switch in Cancer Growth

The KRAS gene belongs to the RAS family of oncogenes. In normal physiology, the KRAS protein functions as an on-off switch: it activates temporarily in response to external signals, instructs the cell to divide, and then rapidly turns itself off. This regulated cycle ensures that healthy tissues grow and repair only when necessary.

When a somatic mutation occurs in the KRAS gene—most commonly at codons 12, 13, or 61—the resulting protein cannot switch back to its inactive conformation. This permanent 'on' switch drives continuous downstream signalling through pathways such as MAPK/ERK, fuelling cancer proliferation, promoting tumour survival, and preventing normal programmed cell death (apoptosis).

Testing for KRAS mutations is essential for modern precision medicine. In cancers like colorectal cancer, the presence of a KRAS mutation indicates that treatments blocking the upstream epidermal growth factor receptor (EGFR) will be ineffective, sparing patients unnecessary toxicity. Furthermore, recent scientific breakthroughs have yielded targeted medications specifically designed to disable certain KRAS variants, fundamentally transforming treatment options.

KRAS status is identified through molecular testing of tumour tissue obtained via biopsy or surgery, using next-generation sequencing (NGS) panels or polymerase chain reaction (PCR) assays. In some cases, circulating tumour DNA (ctDNA) extracted from a blood sample—known as a liquid biopsy—can detect KRAS mutations without invasive tissue sampling.

KRAS mutations are among the most common genomic drivers in cancer. They are found in approximately 90% of pancreatic adenocarcinomas, 40% to 50% of colorectal cancers, and roughly 25% to 30% of non-small cell lung cancers (NSCLC, especially adenocarcinoma). They also appear less frequently in ovarian and endometrial cancers.

For decades, KRAS was considered 'undruggable', but specific inhibitors now exist. Direct KRAS G12C inhibitors (such as sotorasib and adagrasib) are approved for advanced NSCLC and studied in colorectal cancer. Conversely, in metastatic colorectal cancer, a mutated KRAS gene generally precludes the use of anti-EGFR antibody therapies like cetuximab or panitumumab.