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The Importance of KRAS and BRAF Testing in Colorectal Cancer

EGFR Signaling Pathway

KRAS and BRAF Mechanisms in Action

  • Anti-EGFR therapies are commonly used in treating patients with metastatic colorectal cancer.
  • These therapies heavily rely on blocking the EGFR signaling pathway
  • Recent data strongly suggest the evaluation of downstream markers, such as KRAS and BRAF, are important in selecting which patients will respond to therapy
  • Patients with mutations in the KRAS and BRAF oncogene are less likely to respond to anti-EGFR therapies
  • Both KRAS and BRAF are prone to mutations in sporadic colorectal carcinomas (CRC)
  • The combined mutational analysis of both KRAS and BRAF could be used to prospectively select metastatic colorectal cancer patients most likely to benefit from EGFR-targeted MoAb treatment. Monoclonal antibodies approved to treat mCRC
  • Avastin® (bevacizumab), a monoclonal antibody and anti-angiogenesis drug, blocks the growth of blood vessels to the tumor
  • Erbitux® (cetuximab) and Vectibix® (panitumumab) block the effect of hormone-like factors that promote cancer cell growth and binds specifically to the human epidermal growth factor receptor (EGFR)
  • Both Erbitux (cetuximab) and Vectibix (panitumumab) have proven to be effective in providing clinical benefit in approximately 10% to 20% of patients

Metastatic Colorectal Cancer Disease Overview

  • An estimated 150,000 cases of colorectal cancer are expected to occur in 2008
  • Colorectal cancer is the third most common cancer and second most common cause of cancer related deaths
  • An estimated 49,960 deaths from colon and rectal cancer are expected to occur in 2008, accounting for nine percent of all cancer deaths
  • Patients with metastatic colorectal cancer (mCRC) have a 5-year survival rate of less than 10%

KRAS and BRAF Mutation Analysis

KRAS and BRAF Testing is Essential to Anti-EGFR Therapy