The role of senescence and immortalization in carcinogenesis.

Normal somatic cells are able to divide only a limited number of times before they become senescent. The occurrence of intratumoral cell death and the need for clonal evolution mean that many more cell divisions are required for tumorigenesis than is possible unless cells breach the senescence proliferation barrier and become immortalized. Senescence may therefore be a major tumor suppressor mechanism. During the past decade the study of senescence and immortalization has entered the mainstream of cancer research. A major reason for the current interest in this subject is the observation that most cancers have an activated telomere maintenance mechanism, a marker of immortalization. It has also been found that some of the most common genetic changes known to occur in cancer have a key role in the immortalization process.