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