PS07. MOLECULAR ASPECTS OF COLORECTAL CANCER MANAGEMENT ALEKSANDAR J. DIMOVSKI1, T. Josifovski2, N. Petrusevska3
1) Faculty of Pharmacy, University "Sts.Cyril and Methodius", Skopje, R.Macedonia; 2) Clinic for Abdominal Surgery, Clinical Centre, Faculty of Medicine, University "Sts.Cyril and Methodius", Skopje, R.Macedonia; 3) Institute of Radiotherapy and Oncology, Clinical Centre , Faculty of Medicine, University "Sts.Cyril and Methodius", Skopje, R.Macedonia e-mail: adimovski@ff.ukim.edu.mk
*Corresponding Author:
page: 18

Abstract

Colorectal cancer (CRC) is the second to the fourth most common cancer in industrialized countries. The prognosis for patients with CRC is heavily dependent on stage at diagnosis: 5-year survival is over 90% for Dukeís stage A, but only 5% for Dukeís stage D. Early diagnosis is therefore important. The development of an accurate molecular classification for colorectal cancers is potentially of great importance for prevention strategies, therapeutic efficacy, and transferability of clinical trial results.

Genetics has a key role in predisposition to CRC and in its initiation and progression. The mechanisms involved in genetic predisposition to CRC ó that is, the germline changes that precede, control, accelerate or inhibit the well-known sequence of somatic events leading to the development of CRC have been studied extensively. High-penetrance mutations in several genes have been identified that contribute to the two well characterized hereditary colorectal cancer syndromes: familial adenomatous polyposis (FAP) and hereditary non-polyposis colorectal cancer (HNPCC) or Lynch syndrome. The role of these mutations in cancer pathogenesis is well understood and their detection is successfully used in clinical diagnosis. Specific guidelines for diagnosis, management, counseling and follow-up of patients and their relatives have been developed that should lead to more effective management of these high-risk individuals. In stark contrast, our understanding of the influence of low-penetrance mutations that account for most of the remaining familial cases of colorectal cancer, as well as an unknown proportion of sporadic cases, is far less advanced, although several variants in metabolic enzymes, cell cycle control, mismatch repair and/or cell signaling have been described.

Despite radical surgery, more than half of CRC patients develop metastases, and palliative chemotherapy has been utilized to alleviate symptoms and prolong survival. The availability of newer and more efficacious agents over the last few years has seen an improvement in median overall survival in these patients. Nonetheless, the success of chemotherapy is still far from perfect, as tumor response is only observed in ~50% of patients and at the expense of toxicities, which in most subjects are mild to moderate but for other patients may be unpredictable and severe. Over the past few years, intense research efforts have focused on developing molecular biomarkers that could predict response to these various agents. Molecular markers have the potential both to improve our assessment of a patientís outlook after surgery if left untreated and, more innovatively and usefully, to assess the likely effect of adjuvant treatment upon that outlook.




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