Apoptosis in colorectal tumorigenesis and chemotherapy

Abstract

Colorectal cancer is the second most common cancer in the western world. At least 40% of colorectal cancer patients develop metastases; chemotherapy alone or in combination with radiotherapy is usually used as adjuvant treatment for advanced disease. Unfortunately adjuvant treatments are often ineffective due to the development of resistance. A major contributor to chemo-resistance is the inhibition or avoidance of apoptosis. This chapter reviews the genetic mutations in colorectal tumorigenesis; the alterations of apoptosis in colorectal cancer progression; and the relationship between mutations and apoptotic changes. The factors which affect and regulate apoptosis in colorectal cancer development are evaluated. The dysfunction in different apoptotic pathways through which colorectal cancer cells develop resistance to chemotherapies is discussed. Finally the potential molecular targets and therapeutic strategies designed against these targets are proposed.