Senescence in Oncogenesis: From Molecular Mechanisms to Therapeutic Opportunities

Abstract

Somatic non stem cells show a spontaneous decline in growth rate in continuous culture related to an increasing number of population doublings, eventually terminating in a quiescent but viable state now known as replicative senescence. These cells show clear and distinctive morphological, physiological and biochemical characteristics. Moreover, the senescent phenotype is associated with a typical gene-expression profi le. Similar behaviour has since then been observed in a wide variety of normal cells, and it is now widely accepted that normal somatic cells have an intrinsically limited proliferative lifespan, even under ideal growth conditions. Cells displaying characteristics of senescent cells, however, can be also observed in response to other stimuli, such as oncogenic stress, DNA damage or cytotoxic drugs. These non-proliferative characteristics prompted the scientists to look for therapies that can induce the senescent phenotype in tumor cells as therapeutic approach. Keywords The Biology of Cellular SenescenceOver 40 years ago, Hayfl ick ( 1965 ) established that human diploid fi broblasts show a spontaneous decline in growth rate in continuous culture related not to elapsed time but to an increasing number of population doublings, eventually terminating in a quiescent but viable state now known as replicative senescence . These cells show clear and distinctive characteristics. Similar behaviour has since then been observed in a wide variety of normal cells, and it is now widely accepted (Hanahan and Weinberg 2000 ) that normal somatic cells have an intrinsically limited proliferative