Chapter 2 - Premalignant lesions and cellular senescence

Abstract

Precancerous lesions represent a morphologically altered tissue in which cancer is more likely to develop. Numerous premalignant lesions developing in human organs have been described. They are widely recognized as a vital part of the multistep process of carcinogenesis and reflect alterations at the molecular level. Oncogenic signaling leads eventually either to death of transformed cells or induction of Oncogene-Induced Senescence (OIS), a defense mechanism that acts as a biological barrier against cancer progression from its earliest stages. OIS has been demonstrated to some extent in precancerous lesions resulting in delay or inhibition of tumorigenesis. On the other hand and on a long-term basis, OIS can promote the initiation and development of cancer via an autocrine/paracrine secretory function termed senescence-associated secretory phenotype (SASP). Increasing in vitro evidence supports the notion that the “dark” side of OIS can be fueled by additional mechanisms driving “escape” from senescence. Given this bimodal behavior in cancer, the importance of accurate identification of senescent cells in human tissues emerges as a crucial aspect. Developments toward this direction will further clarify the role of OIS, allowing putatively the development of therapeutic interventions in settings where their elimination will be proven beneficial but may also serve as valuable tools for diagnostic purposes.