Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Opinion
  • Published:

Pro-senescence therapy for cancer treatment

Abstract

Abundant evidence points to a crucial physiological role for cellular senescence in combating tumorigenesis. Thus, the engagement of senescence may represent a key component for therapeutic intervention in the eradication of cancer. In this Opinion article, we focus on concepts that are relevant to a pro-senescence approach to therapy and we propose potential therapeutic strategies that aim to enhance the pro-senescence response in tumours.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Differential senescence responses.
Figure 2: Strategies for the therapeutic activation and enhancement of senescence.

Similar content being viewed by others

References

  1. Hayflick, L. The limited in vitro lifetime of human diploid cell strains. Exp. Cell Res. 37, 614–636 (1965).

    Article  CAS  PubMed  Google Scholar 

  2. Di Micco, R., Fumagalli, M. & d'Adda di Fagagna, F. Breaking news: high-speed race ends in arrest-how oncogenes induce senescence. Trends Cell Biol. 17, 529–536 (2007).

    Article  CAS  PubMed  Google Scholar 

  3. Chen, Z. et al. Crucial role of p53-dependent cellular senescence in suppression of Pten-deficient tumorigenesis. Nature 436, 725–730 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Courtois-Cox, S. et al. A negative feedback signaling network underlies oncogene-induced senescence. Cancer Cell 10, 459–472 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Shamma, A. et al. Rb regulates DNA damage response and cellular senescence through E2F-dependent suppression of N-ras isoprenylation. Cancer Cell 15, 255–269 (2009).

    Article  CAS  PubMed  Google Scholar 

  6. Braig, M. et al. Oncogene-induced senescence as an initial barrier in lymphoma development. Nature 436, 660–665 (2005).

    Article  CAS  PubMed  Google Scholar 

  7. Collado, M. et al. Tumour biology: senescence in premalignant tumours. Nature 436, 642 (2005).

    Article  CAS  PubMed  Google Scholar 

  8. Lazzerini Denchi, E., Attwooll, C., Pasini, D. & Helin, K. Deregulated E2F activity induces hyperplasia and senescence-like features in the mouse pituitary gland. Mol. Cell Biol. 25, 2660–2672 (2005).

    Article  PubMed  CAS  Google Scholar 

  9. Michaloglou, C. et al. BRAFE600-associated senescence-like cell cycle arrest of human naevi. Nature 436, 720–724 (2005).

    Article  CAS  PubMed  Google Scholar 

  10. Bartkova, J. et al. Oncogene-induced senescence is part of the tumorigenesis barrier imposed by DNA damage checkpoints. Nature 444, 633–637 (2006).

    Article  CAS  PubMed  Google Scholar 

  11. Fujita, K. et al. p53 isoforms Δ133p53 and p53β are endogenous regulators of replicative cellular senescence. Nature Cell Biol. 11, 1135–1142 (2009).

    Article  CAS  PubMed  Google Scholar 

  12. Kuilman, T. et al. Oncogene-induced senescence relayed by an interleukin-dependent inflammatory network. Cell 133, 1019–1031 (2008).

    Article  CAS  PubMed  Google Scholar 

  13. Collado, M. & Serrano, M. Senescence in tumours: evidence from mice and humans. Nature Rev. Cancer 10, 51–57 (2010).

    Article  CAS  Google Scholar 

  14. Kuilman, T., Michaloglou, C., Mooi, W. J. & Peeper, D. S. The essence of senescence. Genes Dev. 24, 2463–2479 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Harley, C. B., Futcher, A. B. & Greider, C. W. Telomeres shorten during ageing of human fibroblasts. Nature 345, 458–460 (1990).

    Article  CAS  PubMed  Google Scholar 

  16. Bodnar, A. G. et al. Extension of life-span by introduction of telomerase into normal human cells. Science 279, 349–352 (1998).

    Article  CAS  PubMed  Google Scholar 

  17. Vaziri, H. & Benchimol, S. Reconstitution of telomerase activity in normal human cells leads to elongation of telomeres and extended replicative life span. Curr. Biol. 8, 279–282 (1998).

    Article  CAS  PubMed  Google Scholar 

  18. Dickson, M. A. et al. Human keratinocytes that express hTERT and also bypass a p16(INK4a)-enforced mechanism that limits life span become immortal yet retain normal growth and differentiation characteristics. Mol. Cell Biol. 20, 1436–1447 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. MacKenzie, K. L., Franco, S., May, C., Sadelain, M. & Moore, M. A. Mass cultured human fibroblasts overexpressing hTERT encounter a growth crisis following an extended period of proliferation. Exp. Cell Res. 259, 336–350 (2000).

    Article  CAS  PubMed  Google Scholar 

  20. d'Adda di Fagagna, F. et al. A DNA damage checkpoint response in telomere-initiated senescence. Nature 426, 194–198 (2003).

    Article  CAS  PubMed  Google Scholar 

  21. Kiyono, T. et al. Both Rb/p16INK4a inactivation and telomerase activity are required to immortalize human epithelial cells. Nature 396, 84–88 (1998).

    Article  CAS  PubMed  Google Scholar 

  22. Blasco, M. A., Funk, W., Villeponteau, B. & Greider, C. W. Functional characterization and developmental regulation of mouse telomerase RNA. Science 269, 1267–1270 (1995).

    Article  CAS  PubMed  Google Scholar 

  23. Blasco, M. A. et al. Telomere shortening and tumor formation by mouse cells lacking telomerase RNA. Cell 91, 25–34 (1997).

    Article  CAS  PubMed  Google Scholar 

  24. Artandi, S. E. et al. Telomere dysfunction promotes non-reciprocal translocations and epithelial cancers in mice. Nature 406, 641–645 (2000).

    Article  CAS  PubMed  Google Scholar 

  25. Deng, Y., Chan, S. S. & Chang, S. Telomere dysfunction and tumour suppression: the senescence connection. Nature Rev. Cancer 8, 450–458 (2008).

    Article  CAS  Google Scholar 

  26. Artandi, S. E. & DePinho, R. A. A critical role for telomeres in suppressing and facilitating carcinogenesis. Curr. Opin. Genet. Dev. 10, 39–46 (2000).

    Article  CAS  PubMed  Google Scholar 

  27. Serrano, M., Lin, A. W., McCurrach, M. E., Beach, D. & Lowe, S. W. Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a. Cell 88, 593–602 (1997).

    Article  CAS  PubMed  Google Scholar 

  28. Di Micco, R. et al. Oncogene-induced senescence is a DNA damage response triggered by DNA hyper-replication. Nature 444, 638–642 (2006).

    Article  CAS  PubMed  Google Scholar 

  29. Moiseeva, O., Mallette, F. A., Mukhopadhyay, U. K., Moores, A. & Ferbeyre, G. DNA damage signaling and p53-dependent senescence after prolonged beta-interferon stimulation. Mol. Biol. Cell 17, 1583–1592 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. d'Adda di Fagagna, F. Living on a break: cellular senescence as a DNA-damage response. Nature Rev. Cancer 8, 512–522 (2008).

    Article  CAS  Google Scholar 

  31. Ferbeyre, G. et al. PML is induced by oncogenic ras and promotes premature senescence. Genes Dev. 14, 2015–2027 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Wei, W., Hemmer, R. M. & Sedivy, J. M. Role of p14ARF in replicative and induced senescence of human fibroblasts. Mol. Cell Biol. 21, 6748–6757 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Brookes, S. et al. INK4a-deficient human diploid fibroblasts are resistant to RAS-induced senescence. EMBO J. 21, 2936–2945 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Ohtani, N. et al. Opposing effects of Ets and Id proteins on p16INK4a expression during cellular senescence. Nature 409, 1067–1070 (2001).

    Article  CAS  PubMed  Google Scholar 

  35. Bracken, A. P. et al. The Polycomb group proteins bind throughout the INK4A-ARF locus and are disassociated in senescent cells. Genes Dev. 21, 525–530 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Sarkisian, C. J. et al. Dose-dependent oncogene-induced senescence in vivo and its evasion during mammary tumorigenesis. Nature Cell Biol. 9, 493–505 (2007).

    Article  CAS  PubMed  Google Scholar 

  37. Dankort, D. et al. A new mouse model to explore the initiation, progression, and therapy of BRAFV600E-induced lung tumors. Genes Dev. 21, 379–384 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Dhomen, N. et al. Oncogenic Braf induces melanocyte senescence and melanoma in mice. Cancer Cell 15, 294–303 (2009).

    Article  CAS  PubMed  Google Scholar 

  39. Alimonti, A. et al. A novel type of cellular senescence that can be enhanced in mouse models and human tumor xenografts to suppress prostate tumorigenesis. J. Clin. Invest. 120, 681–693.

  40. Nardella, C. et al. Differential requirement of mTOR in postmitotic tissues and tumorigenesis. Sci. Signal 2, ra2 (2009).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  41. Chen, Z. et al. Differential p53-independent outcomes of p19(Arf) loss in oncogenesis. Sci. Signal 2, ra44 (2009).

    PubMed  PubMed Central  Google Scholar 

  42. Palmero, I., Pantoja, C. & Serrano, M. p19ARF links the tumour suppressor p53 to Ras. Nature 395, 125–126 (1998).

    Article  CAS  PubMed  Google Scholar 

  43. Song, M. S. et al. Nuclear PTEN regulates the APC-CDH1 tumor-suppressive complex in a phosphatase-independent manner. Cell 144, 187–199 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Ding, Z. et al. SMAD4-dependent barrier constrains prostate cancer growth and metastatic progression. Nature 470, 269–273 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Yilmaz, O. H. et al. Pten dependence distinguishes haematopoietic stem cells from leukaemia-initiating cells. Nature 441, 475–482 (2006).

    Article  CAS  PubMed  Google Scholar 

  46. Stanger, B. Z. et al. Pten constrains centroacinar cell expansion and malignant transformation in the pancreas. Cancer Cell 8, 185–195 (2005).

    Article  CAS  PubMed  Google Scholar 

  47. Di Micco, R. et al. Interplay between oncogene-induced DNA damage response and heterochromatin in senescence and cancer. Nature Cell Biol. 13, 292–302 (2011).

    Article  CAS  PubMed  Google Scholar 

  48. Donnenberg, V. S. & Donnenberg, A. D. Multiple drug resistance in cancer revisited: the cancer stem cell hypothesis. J. Clin. Pharmacol. 45, 872–877 (2005).

    Article  CAS  PubMed  Google Scholar 

  49. Vassilev, L. T. et al. In vivo activation of the p53 pathway by small-molecule antagonists of MDM2. Science 303, 844–848 (2004).

    Article  CAS  PubMed  Google Scholar 

  50. Wu, C. H. et al. Cellular senescence is an important mechanism of tumor regression upon c-Myc inactivation. Proc. Natl Acad. Sci. USA 104, 13028–13033 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Felsher, D. W. Oncogene addiction versus oncogene amnesia: perhaps more than just a bad habit? Cancer Res. 68, 3081–3086 (2008).

    Article  CAS  PubMed  Google Scholar 

  52. Weinberg, R. A. The retinoblastoma protein and cell cycle control. Cell 81, 323–330 (1995).

    Article  CAS  PubMed  Google Scholar 

  53. Malumbres, M. et al. Cyclin-dependent kinases: a family portrait. Nature Cell Biol. 11, 1275–1276 (2009).

    Article  CAS  PubMed  Google Scholar 

  54. Chicas, A. et al. Dissecting the unique role of the retinoblastoma tumor suppressor during cellular senescence. Cancer Cell 17, 376–387 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Lin, H. K. et al. Skp2 targeting suppresses tumorigenesis by Arf-p53-independent cellular senescence. Nature 464, 374–379 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Chabner, B. A. & Roberts, T. G. Jr. Timeline: Chemotherapy and the war on cancer. Nature Rev. Cancer 5, 65–72 (2005).

    Article  CAS  Google Scholar 

  57. Xue, W. et al. Senescence and tumour clearance is triggered by p53 restoration in murine liver carcinomas. Nature 445, 656–660 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Roninson, I. B. Tumor cell senescence in cancer treatment. Cancer Res. 63, 2705–2715 (2003).

    CAS  PubMed  Google Scholar 

  59. Roberson, R. S., Kussick, S. J., Vallieres, E., Chen, S. Y. & Wu, D. Y. Escape from therapy-induced accelerated cellular senescence in p53-null lung cancer cells and in human lung cancers. Cancer Res. 65, 2795–2803 (2005).

    Article  CAS  PubMed  Google Scholar 

  60. te Poele, R. H., Okorokov, A. L., Jardine, L., Cummings, J. & Joel, S. P. DNA damage is able to induce senescence in tumor cells in vitro and in vivo. Cancer Res. 62, 1876–1883 (2002).

    CAS  PubMed  Google Scholar 

  61. Sidi, R. et al. Induction of senescence markers after neo-adjuvant chemotherapy of malignant pleural mesothelioma and association with clinical outcome: an exploratory analysis. Eur. J. Cancer 47, 326–332 (2011).

    Article  CAS  PubMed  Google Scholar 

  62. Druker, B. J. et al. Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia. N. Engl. J. Med. 344, 1031–1037 (2001).

    Article  CAS  PubMed  Google Scholar 

  63. Soignet, S. L. et al. Complete remission after treatment of acute promyelocytic leukemia with arsenic trioxide. N. Engl. J. Med. 339, 1341–1348 (1998).

    Article  CAS  PubMed  Google Scholar 

  64. Slamon, D. J. et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N. Engl. J. Med. 344, 783–792 (2001).

    Article  CAS  PubMed  Google Scholar 

  65. Carracedo, A. et al. Inhibition of mTORC1 leads to MAPK pathway activation through a PI3K-dependent feedback loop in human cancer. J. Clin. Invest. 118, 3065–3074 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  66. Carracedo, A. & Pandolfi, P. P. The PTEN-PI3K pathway: of feedbacks and cross-talks. Oncogene 27, 5527–5541 (2008).

    Article  CAS  PubMed  Google Scholar 

  67. Luo, J. et al. A genome-wide RNAi screen identifies multiple synthetic lethal interactions with the Ras oncogene. Cell 137, 835–848 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Puyol, M. et al. A synthetic lethal interaction between K-Ras oncogenes and Cdk4 unveils a therapeutic strategy for non-small cell lung carcinoma. Cancer Cell 18, 63–73 (2010).

    Article  CAS  PubMed  Google Scholar 

  69. Campaner, S. et al. Cdk2 suppresses cellular senescence induced by the c-myc oncogene. Nature Cell Biol. 12, 54–59 (2010).

    Article  CAS  PubMed  Google Scholar 

  70. Dimri, G. P. et al. A biomarker that identifies senescent human cells in culture and in aging skin in vivo. Proc. Natl Acad. Sci. USA 92, 9363–9367 (1995).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Debacq-Chainiaux, F., Erusalimsky, J. D., Campisi, J. & Toussaint, O. Protocols to detect senescence-associated beta-galactosidase (SA-betagal) activity, a biomarker of senescent cells in culture and in vivo. Nature Protoc 4, 1798–1806 (2009).

    Article  CAS  Google Scholar 

  72. Young, A. P. et al. VHL loss actuates a HIF-independent senescence programme mediated by Rb and p400. Nature Cell Biol. 10, 361–369 (2008).

    Article  CAS  PubMed  Google Scholar 

  73. Xu, M. et al. Beta-catenin expression results in p53-independent DNA damage and oncogene-induced senescence in prelymphomagenic thymocytes in vivo. Mol. Cell Biol. 28, 1713–1723 (2008).

    Article  CAS  PubMed  Google Scholar 

  74. Ventura, A. et al. Restoration of p53 function leads to tumour regression in vivo. Nature 445, 661–665 (2007).

    Article  CAS  PubMed  Google Scholar 

  75. Tung, C. H. et al. In vivo imaging of beta-galactosidase activity using far red fluorescent switch. Cancer Res. 64, 1579–1583 (2004).

    Article  CAS  PubMed  Google Scholar 

  76. Acosta, J. C. et al. Chemokine signaling via the CXCR2 receptor reinforces senescence. Cell 133, 1006–1018 (2008).

    Article  CAS  PubMed  Google Scholar 

  77. Coppe, J. P. et al. Senescence-associated secretory phenotypes reveal cell-nonautonomous functions of oncogenic RAS and the p53 tumor suppressor. PLoS Biol. 6, 2853–2868 (2008).

    Article  CAS  PubMed  Google Scholar 

  78. Wajapeyee, N., Serra, R. W., Zhu, X., Mahalingam, M. & Green, M. R. Oncogenic BRAF induces senescence and apoptosis through pathways mediated by the secreted protein IGFBP7. Cell 132, 363–374 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Kuilman, T. & Peeper, D. S. Senescence-messaging secretome: SMS-ing cellular stress. Nature Rev. Cancer 9, 81–94 (2009).

    Article  CAS  Google Scholar 

  80. Joyce, J. A. & Pollard, J. W. Microenvironmental regulation of metastasis. Nature Rev. Cancer 9, 239–252 (2009).

    Article  CAS  Google Scholar 

  81. Coppe, J. P., Desprez, P. Y., Krtolica, A. & Campisi, J. The senescence-associated secretory phenotype: the dark side of tumor suppression. Annu. Rev. Pathol. 5, 99–118 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Rakhra, K. et al. CD4+ T cells contribute to the remodeling of the microenvironment required for sustained tumor regression upon oncogene inactivation. Cancer Cell 18, 485–498 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Gattinoni, L., Powell, D. J., Jr., Rosenberg, S. A. & Restifo, N. P. Adoptive immunotherapy for cancer: building on success. Nature Rev. Immunol. 6, 383–393 (2006).

    Article  CAS  Google Scholar 

  84. Vazquez, A., Bond, E. E., Levine, A. J. & Bond, G. L. The genetics of the p53 pathway, apoptosis and cancer therapy. Nature Rev. Drug Discov. 7, 979–987 (2008).

    Article  CAS  Google Scholar 

  85. Bullock, A. N. & Fersht, A. R. Rescuing the function of mutant p53. Nature Rev. Cancer 1, 68–76 (2001).

    Article  CAS  Google Scholar 

  86. Bykov, V. J. et al. Restoration of the tumor suppressor function to mutant p53 by a low-molecular-weight compound. Nature Med. 8, 282–288 (2002).

    Article  CAS  PubMed  Google Scholar 

  87. Peng, Y., Li, C., Chen, L., Sebti, S. & Chen, J. Rescue of mutant p53 transcription function by ellipticine. Oncogene 22, 4478–4487 (2003).

    Article  CAS  PubMed  Google Scholar 

  88. Campisi, J. & d'Adda di Fagagna, F. Cellular senescence: when bad things happen to good cells. Nature Rev. Mol. Cell Biol. 8, 729–740 (2007).

    Article  CAS  Google Scholar 

  89. Hengst, L. & Reed, S. I. Translational control of p27Kip1 accumulation during the cell cycle. Science 271, 1861–1864 (1996).

    Article  CAS  PubMed  Google Scholar 

  90. Chu, I. M., Hengst, L. & Slingerland, J. M. The Cdk inhibitor p27 in human cancer: prognostic potential and relevance to anticancer therapy. Nature Rev. Cancer 8, 253–267 (2008).

    Article  CAS  Google Scholar 

  91. Senderowicz, A. M. Novel small molecule cyclin-dependent kinases modulators in human clinical trials. Cancer Biol. Ther. 2, S84–95 (2003).

    Article  CAS  PubMed  Google Scholar 

  92. Schmitt, C. A. et al. A senescence program controlled by p53 and p16INK4a contributes to the outcome of cancer therapy. Cell 109, 335–346 (2002).

    Article  CAS  PubMed  Google Scholar 

  93. Yin, X., Giap, C., Lazo, J. S. & Prochownik, E. V. Low molecular weight inhibitors of Myc-Max interaction and function. Oncogene 22, 6151–6159 (2003).

    Article  CAS  PubMed  Google Scholar 

  94. Wang, H. et al. Improved low molecular weight Myc-Max inhibitors. Mol. Cancer Ther. 6, 2399–2408 (2007).

    Article  CAS  PubMed  Google Scholar 

  95. Huang, M. J., Cheng, Y. C., Liu, C. R., Lin, S. & Liu, H. E. A small-molecule c-Myc inhibitor, 10058-F4, induces cell-cycle arrest, apoptosis, and myeloid differentiation of human acute myeloid leukemia. Exp. Hematol. 34, 1480–1489 (2006).

    Article  CAS  PubMed  Google Scholar 

  96. Gomez-Curet, I. et al. c-Myc inhibition negatively impacts lymphoma growth. J. Pediatr. Surg. 41, 207–211 (2006).

    Article  Google Scholar 

  97. Trotman, L. C. et al. Pten dose dictates cancer progression in the prostate. PLoS Biol. 1, E59 (2003).

    Article  PubMed  PubMed Central  Google Scholar 

  98. Harley, C. B. et al. Telomerase, cell immortality, and cancer. Cold Spring Harb. Symp. Quant. Biol. 59, 307–315 (1994).

    Article  CAS  PubMed  Google Scholar 

  99. Kelland, L. Targeting the limitless replicative potential of cancer: the telomerase/telomere pathway. Clin. Cancer Res. 13, 4960–4963 (2007).

    Article  CAS  PubMed  Google Scholar 

  100. Harley, C. B. Telomerase and cancer therapeutics. Nature Rev. Cancer 8, 167–179 (2008).

    Article  CAS  Google Scholar 

  101. Schlomm, T. et al. Clinical significance of p53 alterations in surgically treated prostate cancers. Mod. Pathol. 21, 1371–1378 (2008).

    Article  CAS  PubMed  Google Scholar 

  102. Efimova, E. V. et al. Poly(ADP-ribose) polymerase inhibitor induces accelerated senescence in irradiated breast cancer cells and tumors. Cancer Res. 70, 6277–6282 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Poliseno, L. et al. The proto-oncogene LRF is under post-transcriptional control of MiR-20a: implications for senescence. PLoS One 3, e2542 (2008).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  104. Gewinner, C. et al. Evidence that inositol polyphosphate 4-phosphate type II is a tumor supressor that inhibits PI3K signalling. Cancer Cell 16, 115–125 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The authors would like to acknowledge current members of the Pandolfi laboratory for critical discussion and previous members who have contributed to senescence work. Senescence-related work within the Pandolfi laboratory has been supported by US National Institutes of Health grants R01CA082328 and U01CA141496 (Mouse Models of Human Cancer Consortium-supported), and by a Prostate Cancer Foundation Creativity Grant in support of highly creative prostate cancer research proposals not fundable by other existing mechanisms.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Pier Paolo Pandolfi.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Related links

Rights and permissions

Reprints and permissions

About this article

Cite this article

Nardella, C., Clohessy, J., Alimonti, A. et al. Pro-senescence therapy for cancer treatment. Nat Rev Cancer 11, 503–511 (2011). https://doi.org/10.1038/nrc3057

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrc3057

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing