Discovery of predictive biomarker candidates for intrinsic resistance to FOLFOX chemotherapy in colon cancer using a Top Down LC-MALDI approach

Colorectal cancer is the third most commonly diagnosed cancer in males and the second in females, with over 1.2 million new cancer cases and 608,700 cancer related deaths in 2008 [1]. Despite the advances being made in early detection of colorectal cancer, approximately half of all patients develop metastatic disease [2]. The prognosis for these patients is poor, although palliative chemotherapy has been shown to be able to prolong survival and to improve the quality of life compared with the best supportive care [3]. Chemoresistance of cancer cells to chemotherapeutics is a main obstacle in chemotherapy to a successful outcome in first line therapy. It has been hypothesized that selection pressure resulting from tumor internal evolution can lead to subpopulations of cell clones, carrying certain cellular mechanism that can be summarized under the term “intrinsic chemoresistance.” Cellular mechanisms of intrinsic chemo resistance are mainly characterized by the fact that they lead to increased tolerance of cancer cells to chemotherapeutics. These cells are most likely to survive first line chemotherapy and arise as recurrence disease.