Quantifying replicative senescence as a tumor suppressor pathway and a target for cancer therapy
| العنوان: | Quantifying replicative senescence as a tumor suppressor pathway and a target for cancer therapy |
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| المؤلفون: | Natalia L. Komarova, Ignacio A. Rodriguez-Brenes, Dominik Wodarz |
| المصدر: | Scientific Reports Scientific reports, vol 5, iss 1 |
| بيانات النشر: | Nature Publishing Group, 2015. |
| سنة النشر: | 2015 |
| مصطلحات موضوعية: | 0301 basic medicine, Senescence, Telomerase, Cell division, Cell, Population, Biology, Models, Biological, Article, 03 medical and health sciences, Models, Neoplasms, medicine, Humans, Molecular Targeted Therapy, education, Cellular Senescence, Cancer, education.field_of_study, Multidisciplinary, Tumor Suppressor Proteins, Hayflick limit, Biological, medicine.disease, Cell biology, 030104 developmental biology, medicine.anatomical_structure, 5.1 Pharmaceuticals, Cancer research, Development of treatments and therapeutic interventions, Cell aging, Algorithms, Signal Transduction |
| الوصف: | To study quantitatively replicative senescence as a tumor suppressor mechanism, we investigate the distribution of a growing clonal cell population restricted by Hayflick’s limit. We find that in the biologically relevant range of parameters, if the imbalance between cell division and death is moderate or low (high death-to-birth ratio), senescence offers significant protection against cancer by halting abnormal cell proliferation at early pre-diagnostic stages of tumor development. We also find that by the time tumors are typically detected, there is a high probability that telomerase is activated, even if the cell of origin was telomerase negative. Hence, the fact that most cancers are positive for telomerase is not necessarily an indication that cancer originated in a telomerase positive cell. Finally, we discuss how the population dynamics of cells can determine the outcomes of anti-telomerase cancer therapies and provide guidelines on how the model could potentially be applied to develop clinically useful tools to predict the response to treatment by telomerase inhibitors in individual patients. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 2045-2322 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::04242c5e49d2b37d314e96a83a31d594Test http://europepmc.org/articles/PMC4673423Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....04242c5e49d2b37d314e96a83a31d594 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20452322 |
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