ABSTRACT
Introduction An essential acquired capability of the malignant cell through which tumor tissue escapes from the mechanisms of growth control is limitless replicative potential. After a certain period of doubling activity, normal cells in culture enter a senescence process, which ultimately leads to a crisis state with massive cell death. Tumor cells are immortalized and have the capability of unlimited replicative potential, which is acquired during tumorigenesis. Immortalization of tumor cells is due to a balance between telomeres (special chromatin structures at the end of eukaryotic chromosomes, which shorten progressively during cellular replication, resulting in loss of telomere protection and eventual growth arrest) and telomerase (a cellular ribonucleotide enzyme responsible for adding telomere repeats at the end of chromosomes). Telomerase is not detected in most normal tissues, with the exception of germline cells, hematopoietic progenitor cells, and cells of regenerative tissues such as the epidermis and intestinal crypts. Telomerase is reactivated or upregulated in 90% of human tumors, thus bypassing replicative senescence (Figure 6.1). Large differences in constitutive telomerase expression between most adult somatic and tumor tissues, and the critical length of telomere to be reached to trigger loss of viability in the absence of telomerase or reactivation of telomerase in tumor, indicate a window of opportunity for selective antitumor interventions. Another process through which cancer cells acquire a limitless replicative potential or unregulated self-renewal is by cancer stem cells, which are characterized by their capacity to proliferate outside the normal growth-regulating mechanisms and to invade and destroy normal tissues.
