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.
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.
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 – KRASG12C – is estimated to impact more than 70,000 patients with cancer in the U.S. and Europe.
The KRASG12C mutation has been found to occur in approximately:
Identifying a mutation like KRASG12C 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.
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For decades, scientists and medical researchers worked diligently to better understand the role of different mutations in cancer growth,” said Joseph Fiore, vice president and global program lead in Oncology Development. “Given the availability of diagnostic tools, testing for KRAS mutations should be a priority in managing patients diagnosed with certain tumors.
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 KRASG12C, becomes the norm, helping drive toward more informed treatment decisions for patients.
Bristol Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. As global citizens, we work sustainably and responsibly to create a positive impact in the communities where we live and work.