Cell senescence does not stop cancer growth

A collaboration between a cancer biologist (from the University of Milano, Italy) and two physicists (from the National Research Council of Italy and from Cornell University) has shown that cell senescence occurs spontaneously in melanoma cells but does not arrest their growth, which  is sustained by a small population of cancer stem cells. The results published in PLoS Computational Biology explain why it is difficult to treat cancer by inducing senescence.

Normal cells can duplicate for a finite number of times in vitro, after which they turn senescent and stop replicating. Since cancer cells grow indefinitely, it is commonly believed that senescence could act as a barrier for tumor growth and could thus be used to treat cancer.

The investigators followed the long-term evolution of melanoma cell populations, monitoring  the fraction of senescent cells. After three months, growth slowed and most of the cells turned senescent. Yet growth did not stop, but  eventually resumed at the initial rate while senescent cells almost disappeared. The authors modeled the experimental data, using the cancer stem cell hypothesis. The model assumes a small population of cancer cells with  stem cell properties that  are able to self-renew and give rise to more differentiated cells indefinitely and and a larger population of cancer cells that can duplicate only a finite number of times before turning senescent. The model yields an indirect confirmation of the presence of cancer stem cells in melanoma, an issue that is still controversial in the literature.

Since a large fraction of cancer cells are susceptible to senescence, but those cells are irrelevant for tumor growth, the researchers conclude that inducing senescence is unlikely to provide a successful therapeutic strategy. Targeting cancer stem cells would appear to be more promising, but would face challenges from strong resistance to drug induced senescence in these cells.

Paper (Open access):

La Porta CAM, Zapperi S, Sethna JP (2012) Senescent Cells in Growing Tumors: Population Dynamics and Cancer Stem Cells. PLoS Comput Biol 8(1): e1002316. doi:10.1371/journal.pcbi.1002316

http://www.ploscompbiol.org/doi/pcbi.1002316