KRAS, 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.

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%.