**3.2 Serum biomarkers**

56 Biomarker

to cetuximab and PTEN null metastasis had shorter progression free survival, which was even more significant in *KRAS* wild-type patients. In sharp contrast, the PTEN analysis on the primary tumor did not reveal any predictive or prognostic information. Although the relative low concordance rate between the primary and metastatic tumors for PTEN expression could be secondary to selection of clonal populations during metastasis, it could be the subjective nature of immunohistochemistry testing with significant method and observer variability. This consideration and the possible need to analyze PTEN from metastatic tumors may limit the role of PTEN as biomarker in CRC (Dasari & Messersmith,

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,

Pancreatic cancer has the worst prognosis of all gastrointestinal malignancies with the mortality approaching the incidence (Buxbaum & Eloubeidi, 2010)(Bünger et al., 2011). Late clinical presentation, intrinsic biological aggressiveness, and resistance to conventional chemotherapy and radiotherapy represent the predominant reasons for its poor prognosis (Pizzi et al., 2009). This demonstrates an urgent demand for improved screening tools for early detection (Buxbaum & Eloubeidi, 2010)(Bünger et al., 2011). While surveillance is performed in individuals with genetic syndromes, hereditary pancreatitis, and a strong family history there are no clear guidelines for those with clinical risk factors like diabetes mellitus, tobacco use, and chronic pancreatitis (Buxbaum & Eloubeidi, 2010). Pancreatic ductal adenocarcinoma is the most commonly diagnosed pancreatic neoplasm, and reported to be the forth or fifth leading cause of cancer death in Western countries. Diagnosis of pancreatic cancer at early stages is crucial because successful surgical resection remains the only possibility of cure (Ansari et al., 2011). Only 10-30% of pancreatic tumor patients are operated on with curative intent. The expected 5-year survival rate of R0 resected patients with additional adjuvant chemotherapy is about 4-26%. In contrast, for the remaining patients who present with unresectable UICC stage III and IV carcinomas, no curative

2010).

**2.6 Conclusion** 

2010)(De Roock et al., 2011).

**3. Pancreatic cancer** 

**3.1 Introduction** 

Improved screening for early diagnosis is essential in order to increase the rate of curatively resectable carcinomas, thereby ameliorating patient's prognosis. In present clinical practice, screening for pancreatic cancer is based on state-of-the-art imaging or even invasive diagnostics. A relatively non-invasive, cost efficient possibility could be provided by the measurement of disease-specific markers in peripheral blood. A wide range of serum markers has been reported to be elevated in pancreatic cancer patients since the eighties. Despite these many markers or their combinations with high diagnostic potential for pancreatic cancer screening, none of them have achieved the levels of sensitivity and specificity necessary to be recommended as a screening tool for asymptomatic patients in the general population (Bünger et al., 2011)(Xu et al., 2011). Only a few markers have shown promising results in recent studies with CA19-9 being the most widely investigated and evaluated single marker (Bünger et al., 2011).
