KRAS Status Predicts Response to Therapies in Colorectal Cancer Recent findings in a gene mutation may be able to better predict which patients may respond better to anti-EGFR therapies. In the US alone, there are over 150,000 newly diagnosed cases each year. Many of these patients are diagnosed with metastatic colorectal cancer (mCRC). It is the third most common cancer but the second most common cause of cancer-related deaths. Although the number of patients surviving 5-years with advanced stage mCRC remains small, recent advances may be better able to separate out those that respond to novel cytotoxic and biologic agents versus those that don’t respond to these agents. Currently treatments for patients with colorectal cancer include several targeted monoclonal antibodies, as well as conventional chemotherapeutic agents. Bevacizumab (Avastin®), cetuximab (Erbitux®), and panitumumab (Vectibix™), along with conventional chemotherapeutic drugs, are some of the most commonly used agents to treat patients with mCRC. Both cetuximab and panitumumab interact with the epidermal growth factor receptor (EGFR). These drugs fall into a category of agents called anti-EGFR therapies. Recent data now suggests a differential response to anti-EGFR antibody therapy based on mutational status of a major oncogene called KRAS. It is suggested that KRAS mutations can be detected in approximately 30% to 45% of colorectal cancers. The majority of mutations occur at codons 12, 13, and 61 of the KRAS gene, which is located on chromosome 12. The recent data presents evidence showing patients with a mutation in the KRAS gene are much less likely to respond to anti-EGFR therapy than those patients with a normal KRAS gene. As a brief overview, the Ras-Raf-MAPK pathway lies just downstream of EGFR. The hypothesis suggests that a mutation in KRAS could render cells independent of upstream EGFR activation or inhibition of the receptor though anti-EGFR therapies. Several recent studies now show strong correlation of KRAS mutation with response to panitumumab and cetuximab. These studies show compelling evidence that KRAS mutation is a biomarker of non-response to either of these drugs in mCRC patients. Choosing the correct therapy for the patient becomes critical to improving clinical outcomes, unnecessary toxicities, and cost to the patient.
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Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer.
Progress in Personalized Therapy: KRAS Status Predicts Response to First-line Cetuximab for Metastatic Colorectal Cancer
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