Prognostic And Predictive Markers In Colorectal Cancer

This integrated book covers the entire spectrum of cancer biomarkers in development and clinical use. Predictive and prognostic markers are explored in the context of colon cancer, breast cancer, lung cancer, prostate cancer, and GIST. International experts provide insight into toxicity markers and surrogate markers. Attention is also given to biomarker assay development, validation, and strategies. A powerful tool for determining decisions on therapy, selecting drug regimens, monitoring the efficacy of treatment, and performing individualized surveillance, biomarkers represent the forefront of cancer research and treatment. As these technologies become increasingly available for clinical use, this book will be an essential resource for oncologists and translational researchers.

Colorectal cancer has for more than two decades served as the paradigm for the multi-step concept of cancer initiation and progression. Perhaps more than any other organ site, cancer of the colon is extensively characterized at the molecular level. We are now entering a time when molecular classification, rather than histologic classification, of cancer subtypes is driving the development of clinical trials with emerging targeted therapies. The book will focus on the progression from the identification of mutations that drive colorectal cancer initiation and progression to the search for novel therapies to treat the disease.

Since the success in chemical induction of cancer in rabbit's ear skin by K. Yamagiwa in 1915, oncologists of the world have come to believe that they can only solve their problems by means of animal experimen tation. The importance of environmental factors became moreevident in 1935 when T. Yoshida and T. Sasaki introduced azodye hepatocarcino genesis in rats. In the domain of the gastrointestinal tract, T. Sugimura has more recently accumulated enough evidence to indicate that locally active chemical mutagens are carcinogenic. In contrast, principal approaches to colorectal tumors have been quite different: emphasis has been placed on gene identification. Long before cancer of the large bowel was recognized, importance of the roles of adenomatosis coli and its familial occurrence attracted the attention of epidemiologists and geneticists. Morphological characteri zation and analysis of hereditary trends of human material have already bad a long history, and recently detailed analysis of genetic material has become feasible in the wake of rapid development in our knowledge of the oncoviruses, oncogenes, suppressor genes, chromosomal and DNA mapping, molecular mutation and so on. lt is true that in colorectal pathology, and in no other field, these areas of research have been explored more extensively and decisively. The identification of previ ously ill-defined lesions such as precancers and benign neoplasms have been improved because sequential changes can be observed in multiple samples spread over a wide area and followed up in due course.

M. K. Gospodarowicz, P. Hermanek, and D. E. Henson Attention to innovations in cancer treatment has tended to eclipse the importance of prognostic assessment. However, the recognition that prognostic factors often have a greater impact on outcome than available therapies and the proliferation of biochemical, molecular, and genetic markers have resulted in renewed interest in this field. The outcome in patients with cancer is determined by a combination of numerous factors. Presently, the most widely recognized are the extent of disease, histologic type of tumor, and treatment. It has been known for some time that additional factors also influence outcome. These include histologic grade, lymphatic or vascular invasion, mitotic index, performance status, symptoms, and most recently genetic and biochemical markers. It is the aim of this volume to compile those prognostic factors that have emerged as important determinants of outcome for tumors at various sites. This compilation represents the first phase of a more extensive process to integrate all prognostic factors in cancer to further enhance the prediction of outcome following treatment. Certain issues surround ing the assessment and reporting of prognostic factors are also considered. Importance of Prognostic Factors Prognostic factors in cancer often have an immense influence on outcome, while treatment often has a much weaker effect. For example, the influence of the presence of lymph node involvement on survival of patients with metastatic breast cancer is much greater than the effect of adjuvant treatment with tamoxifen in the same group of patients [5].

In 2007, Jeremy Jass proposed a molecular classification of colorectal cancer including KRAS, BRAF, Mismatch Repair, CIMP and MGMT Status. Since then, many prognostic and predictive studies have been published on this topic, mainly focusing on one single molecular marker. The aim of the e-book is to summarize the knowledge in 2014 from a multidisciplinary point of view that can potentially be used as a manual by CRC researchers in every field.