**2.6 Conclusion**

In summary, both MAPK and PI3K pathways are stimulated by EGFR, with important implication for EGFR targeted therapy and future drug development. Current American Society of Clinical Oncology (ASCO) guidelines recommend testing only for *KRAS* mutations in codon 12 and codon 13, in patients being considered for EGFR moAb therapy (Dasari & Messersmith, 2010). However, evidence shows that other molecular alterations, such as *BRAF*, *PIK3CA* (exon-20) mutations or loss of PTEN expression, could preclude response to EGFR moAb. The subjective nature of PTEN assessment, however, is a significant challenge. In addition, new drugs are being developed against numerous targets in these pathways, and many are in early clinical stages. Finally, a better understanding of the functional interactions within RTK-activated intracellular pathways is essential to target the individual tumor and to deliver more effective medical treatment to patients with mCRC. Furthermore, the ability of the cancer cell to develop drug resistance via new mutations or alternative signaling pathways also needs to be addressed by combination therapy, and, if possible, analysis of tumor tissue upon progression (Dasari & Messersmith, 2010)(De Roock et al., 2011).
