The power of biomarker testing: Advancing KRAS research today and tomorrow

In recent decades, scientists identified genes that, when mutated, have the potential to cause cancer – called oncogenes. The most frequently mutated oncogene in solid tumors is KRAS. This oncogene acts as an ‘on-off switch,’ helping regulate how cells grow and divide.

Normally, KRAS directs cells to stop growing. However, when KRAS is mutated, the protein it produces becomes stuck in the “on” position and cannot process guanosine triphosphate (GTP). This triggers downstream signaling that leads cells to continuously generate, initiating and sustaining tumor growth. These cells can potentially develop into aggressive cancers.

Challenges in KRAS research

Scientists involved in drug discovery efforts in oncology were stymied by KRAS for more than 40 years, finding it to be a challenging therapeutic target because of the characteristics of the protein it produces. Among other challenges, the KRAS protein has a smooth surface, providing few pockets for small molecule drugs to bind to.

As a result, for many years, certain patients whose tumors had KRAS mutations were given a poor prognosis. They had few treatment options, as KRAS-mutated cancers do not respond well to chemotherapy.

Importance of biomarker testing

KRAS mutations can be present in solid tumors, including lung, colorectal and pancreatic cancers, which are globally some of the most common cancers. One particular KRAS mutation – KRAS^G12C – is estimated to impact more than 70,000 patients with cancer in the U.S. and Europe.

The KRAS^G12C mutation has been found to occur in approximately:

• 14% of non-small cell lung cancers (NSCLC)
• 3% to 4% of colorectal cancers (CRC)
• 1% to 2% of pancreatic ductal adenocarcinomas (PDAC)

Identifying a mutation like KRAS^G12C through biomarker testing is important as it allows healthcare providers to better understand the specific underlying mechanism of disease. Both the National Comprehensive Cancer Network (NCCN) Guidelines in the U.S. and the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines recommend biomarker testing for certain solid tumors. This knowledge may help guide informed decisions about the best course of action and future disease management.

Shaping the future of research

At Bristol Myers Squibb, we are driven by a deep understanding of disease biology and the complexities of cancer. While we advance the discovery and development of breakthrough treatments in oncology, we look to a future where comprehensive biomarker testing, including for KRAS^G12C, becomes the norm, helping drive toward more informed treatment decisions for patients.