Cited by 867Telomeres, Telomerase, and SenescenceGenetics, Aging, and Longevity in Model OrganismsCell death mechanisms and regulation

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Exploiting senescence for the treatment of cancer

Wang, Liqin, Lankhorst, Lina, Bernards, René·2022·Nature Reviews Cancer

DOI 10.1038/s41568-022-00450-9

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Abstract

Senescence is a cellular response to a variety of stress signals that is characterized by a stable withdrawal from the cell cycle and major changes in cell morphology and physiology. While most research on senescence has been performed on non-cancer cells, it is evident that cancer cells can also mount a senescence response. In this Review, we discuss how senescence can be induced in cancer cells. We describe the distinctive features of senescent cancer cells and how these changes in cellular physiology might be exploited for the selective eradication of these cells (senolysis). We discuss activation of the host immune system as a particularly attractive way to clear senescent cancer cells. Finally, we consider the challenges and opportunities provided by a 'one-two punch' sequential treatment of cancer with pro-senescence therapy followed by senolytic therapy.

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Hallmarks of Cancer: The Next Generation
Hanahan, D., & Weinberg, R. A. (2011) · Cell · doi:10.1016/j.cell.2011.02.013 · Cited by 66,590
The serial cultivation of human diploid cell strains
Hayflick, L., & Moorhead, P. S. (1961) · Experimental Cell Research · doi:10.1016/0014-4827(61)90192-6 · Cited by 8,508
Cisplatin in cancer therapy: Molecular mechanisms of action
Dasari, S., & Bernard Tchounwou, P. (2014) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2014.07.025 · Cited by 5,537
Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a
Serrano, M., Lin, A. W., McCurrach, M. E., Beach, D., & Lowe, S. W. (1997) · Cell · doi:10.1016/s0092-8674(00)81902-9 · Cited by 5,218
The senescence-associated secretory phenotype: the dark side of tumor suppression
Coppé, J.-P., Desprez, P.-Y., Krtolica, A., & Campisi, J. (2010) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev-pathol-121808-102144 · Cited by 5,206
In Vivo Activation of the p53 Pathway by Small-Molecule Antagonists of MDM2
Vassilev, L. T., Vu, B. T., Graves, B., Carvajal, D., Podlaski, F., Filipovic, Z., Kong, N., Kammlott, U., Lukacs, C., Klein, C., et al. (2004) · Science · doi:10.1126/science.1092472 · Cited by 4,661
Cell cycle, CDKs and cancer: a changing paradigm
Malumbres, M., & Barbacid, M. (2009) · Nature Reviews Cancer · doi:10.1038/nrc2602 · Cited by 3,957
Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders
Baker, D. J., Wijshake, T., Tchkonia, T., LeBrasseur, N. K., Childs, B. G., van de Sluis, B., Kirkland, J. L., & van Deursen, J. M. (2011) · Nature · doi:10.1038/nature10600 · Cited by 3,670
Cellular Senescence: Defining a Path Forward
Gorgoulis, V., Adams, P. D., Alimonti, A., Bennett, D. C., Bischof, O., Bishop, C., Campisi, J., Collado, M., Evangelou, K., Ferbeyre, G., et al. (2019) · Cell · doi:10.1016/j.cell.2019.10.005 · Cited by 3,225
ABT-199, a potent and selective BCL-2 inhibitor, achieves antitumor activity while sparing platelets
Souers, A. J., Leverson, J. D., Boghaert, E. R., Ackler, S. L., Catron, N. D., Chen, J., Dayton, B. D., Ding, H., Enschede, S. H., Fairbrother, W. J., et al. (2013) · Nature Medicine · doi:10.1038/nm.3048 · Cited by 3,058
Aging, Cellular Senescence, and Cancer
Campisi, J. (2013) · Annual Review of Physiology · doi:10.1146/annurev-physiol-030212-183653 · Cited by 2,954
Naturally occurring p16Ink4a-positive cells shorten healthy lifespan
Baker, D. J., Childs, B. G., Durik, M., Wijers, M. E., Sieben, C. J., Zhong, J., A. Saltness, R., Jeganathan, K. B., Verzosa, G. C., Pezeshki, A., et al. (2016) · Nature · doi:10.1038/nature16932 · Cited by 2,876
Cellular senescence: from physiology to pathology
Muñoz-Espín, D., & Serrano, M. (2014) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3823 · Cited by 2,818
The role of senescent cells in ageing
van Deursen, J. M. (2014) · Nature · doi:10.1038/nature13193 · Cited by 2,623
Hallmarks of Cellular Senescence
Hernandez-Segura, A., Nehme, J., & Demaria, M. (2018) · Trends in Cell Biology · doi:10.1016/j.tcb.2018.02.001 · Cited by 2,605
The Achilles' heel of senescent cells: from transcriptome to senolytic drugs
Zhu, Y., Tchkonia, T., Pirtskhalava, T., Gower, A. C., Ding, H., Giorgadze, N., Palmer, A. K., Ikeno, Y., Hubbard, G. B., Lenburg, M., et al. (2015) · Aging Cell · doi:10.1111/acel.12344 · Cited by 2,584
Senescence and tumour clearance is triggered by p53 restoration in murine liver carcinomas
Xue, W., Zender, L., Miething, C., Dickins, R. A., Hernando, E., Krizhanovsky, V., Cordon-Cardo, C., & Lowe, S. W. (2007) · Nature · doi:10.1038/nature05529 · Cited by 2,473
Cellular senescence in aging and age-related disease: from mechanisms to therapy
Childs, B. G., Durik, M., Baker, D. J., & van Deursen, J. M. (2015) · Nature Medicine · doi:10.1038/nm.4000 · Cited by 2,363
Topoisomerase I inhibitors: camptothecins and beyond
Pommier, Y. G. (2006) · Nature reviews. Cancer · doi:10.1038/nrc1977 · Cited by 2,362
Senolytics improve physical function and increase lifespan in old age
Xu, M., Pirtskhalava, T., Farr, J. N., Weigand, B. M., Palmer, A. K., Weivoda, M. M., Inman, C. L., Ogrodnik, M. B., Hachfeld, C. M., Fraser, D. G., et al. (2018) · Nature Medicine · doi:10.1038/s41591-018-0092-9 · Cited by 2,287
A complex secretory program orchestrated by the inflammasome controls paracrine senescence
Acosta, J. C., Banito, A., Wuestefeld, T., Georgilis, A., Janich, P., Morton, J. P., Athineos, D., Kang, T.-W., Lasitschka, F., Andrulis, M., et al. (2013) · Nature Cell Biology · doi:10.1038/ncb2784 · Cited by 2,278
Persistent DNA damage signalling triggers senescence-associated inflammatory cytokine secretion
Rodier, F., Coppé, J.-P., Patil, C. K., Hoeijmakers, W. A. M., Muñoz, D. P., Raza, S. R., Freund, A., Campeau, E., Davalos, A. R., & Campisi, J. (2009) · Nature Cell Biology · doi:10.1038/ncb1909 · Cited by 2,232
BRAFE600-associated senescence-like cell cycle arrest of human naevi
Michaloglou, C., Vredeveld, L. C. W., Soengas, M. S., Denoyelle, C., Kuilman, T., van der Horst, C. M. A. M., Majoor, D. M., Shay, J. W., Mooi, W. J., & Peeper, D. S. (2005) · Nature · doi:10.1038/nature03890 · Cited by 2,160
The Interleukin-8 Pathway in Cancer
Waugh, D. J. J., & Wilson, C. (2008) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-07-4843 · Cited by 2,103
Oncogene-Induced Senescence Relayed by an Interleukin-Dependent Inflammatory Network
Kuilman, T., Michaloglou, C., Vredeveld, L. C. W., Douma, S., van Doorn, R., Desmet, C. J., Aarden, L. A., Mooi, W. J., & Peeper, D. S. (2008) · Cell · doi:10.1016/j.cell.2008.03.039 · Cited by 2,086
The essence of senescence: Figure 1.
Kuilman, T., Michaloglou, C., Mooi, W. J., & Peeper, D. S. (2010) · Genes & Development · doi:10.1101/gad.1971610 · Cited by 2,038
Senescence of Activated Stellate Cells Limits Liver Fibrosis
Krizhanovsky, V., Yon, M., Dickins, R. A., Hearn, S., Simon, J., Miething, C., Yee, H., Zender, L., & Lowe, S. W. (2008) · Cell · doi:10.1016/j.cell.2008.09.015 · Cited by 2,027
Crucial role of p53-dependent cellular senescence in suppression of Pten-deficient tumorigenesis
Chen, Z., Trotman, L. C., Shaffer, D., Lin, H.-K., Dotan, Z. A., Niki, M., Koutcher, J. A., Scher, H. I., Ludwig, T., Gerald, W., et al. (2005) · Nature · doi:10.1038/nature03918 · Cited by 1,993
The first 30 years of p53: growing ever more complex.
Levine, A. J., & Oren, M. (2009) · Nature Reviews Cancer · doi:10.1038/nrc2723 · Cited by 1,967
Targeting DNA topoisomerase II in cancer chemotherapy
Nitiss, J. L. (2009) · Nature reviews. Cancer · doi:10.1038/nrc2607 · Cited by 1,861
An Oncogene-Induced DNA Damage Model for Cancer Development
Halazonetis, T. D., Gorgoulis, V. G., & Bartek, J. (2008) · Science · doi:10.1126/science.1140735 · Cited by 1,851
Restoration of p53 function leads to tumour regression in vivo
Ventura, A., Kirsch, D. G., McLaughlin, M. E., Tuveson, D. A., Grimm, J., Lintault, L., Newman, J., Reczek, E. E., Weissleder, R., & Jacks, T. (2007) · Nature · doi:10.1038/nature05541 · Cited by 1,820
Clearance of senescent cells by ABT263 rejuvenates aged hematopoietic stem cells in mice
Chang, J., Wang, Y., Shao, L., Laberge, R.-M., Demaria, M., Campisi, J., Janakiraman, K., Sharpless, N. E., Ding, S., Feng, W., et al. (2016) · Nature Medicine · doi:10.1038/nm.4010 · Cited by 1,819
Chemokine signaling via the CXCR2 receptor reinforces senescence
Acosta, J. C., O'Loghlen, A., Banito, A., Guijarro, M. V., Augert, A., Raguz, S., Fumagalli, M., Da Costa, M., Brown, C., Popov, N., et al. (2008) · Cell · doi:10.1016/j.cell.2008.03.038 · Cited by 1,801
Senescence in Health and Disease
He, S., & Sharpless, N. E. (2017) · Cell · doi:10.1016/j.cell.2017.05.015 · Cited by 1,766
Senescent fibroblasts promote epithelial cell growth and tumorigenesis: A link between cancer and aging
Krtolica, A., Parrinello, S., Lockett, S., Desprez, P.-Y., & Campisi, J. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.211053698 · Cited by 1,730
Senescence surveillance of pre-malignant hepatocytes limits liver cancer development
Kang, T.-W., Yevsa, T., Woller, N., Hoenicke, L., Wuestefeld, T., Dauch, D., Hohmeyer, A., Gereke, M., Rudalska, R., Potapova, A., et al. (2011) · Nature · doi:10.1038/nature10599 · Cited by 1,621
Local clearance of senescent cells attenuates the development of post-traumatic osteoarthritis and creates a pro-regenerative environment
Jeon, O. H., Kim, C., Laberge, R.-M., Demaria, M., Rathod, S., Vasserot, A. P., Chung, J. W., Kim, D. H., Poon, Y., David, N., et al. (2017) · Nature Medicine · doi:10.1038/nm.4324 · Cited by 1,515
DNA Damage Sensing by the ATM and ATR Kinases
Marechal, A., & Zou, L. (2013) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a012716 · Cited by 1,514
CDK4/6 inhibition triggers anti-tumour immunity
Goel, S., DeCristo, M. J., Watt, A. C., BrinJones, H., Sceneay, J., Li, B. B., Khan, N., Ubellacker, J. M., Xie, S., Metzger-Filho, O., et al. (2017) · Nature · doi:10.1038/nature23465 · Cited by 1,513
Senescence in premalignant tumours
Collado, M., Gil, J., Efeyan, A., Guerra, C., Schuhmacher, A. J., Barradas, M., Benguría, A., Zaballos, A., Flores, J. M., Barbacid, M., et al. (2005) · Nature · doi:10.1038/436642a · Cited by 1,482
Reversal of human cellular senescence: roles of the p53 and p16 pathways
Beauséjour, C. M., Krtolica, A., Galimi, F., Narita, M., Lowe, S. W., Yaswen, P., & Campisi, J. (2003) · The EMBO Journal · doi:10.1093/emboj/cdg417 · Cited by 1,457
Targeted Apoptosis of Senescent Cells Restores Tissue Homeostasis in Response to Chemotoxicity and Aging
Baar, M. P., Brandt, R. M. C., Putavet, D. A., Klein, J. D. D., Derks, K. W. J., Bourgeois, B. R. M., Stryeck, S., Rijksen, Y., van Willigenburg, H., Feijtel, D. A., et al. (2017) · Cell · doi:10.1016/j.cell.2017.02.031 · Cited by 1,454
Senescence-associated β-galactosidase is lysosomal β-galactosidase.
Lee, B. Y., Han, J. A., Im, J. S., Morrone, A., Johung, K., Goodwin, E. C., Kleijer, W. J., DiMaio, D., & Hwang, E. S. (2006) · Aging Cell · doi:10.1111/j.1474-9726.2006.00199.x · Cited by 1,444
A Cancer Cell Program Promotes T Cell Exclusion and Resistance to Checkpoint Blockade
Jerby-Arnon, L., Shah, P., Cuoco, M. S., Rodman, C., Su, M.-J., Melms, J. C., Leeson, R., Kanodia, A., Mei, S., Lin, J.-R., et al. (2018) · Cell · doi:10.1016/j.cell.2018.09.006 · Cited by 1,429
Angiogenesis and Inflammation in Peritoneal Dialysis: The Role of Adipocytes
Shi, J., Yu, M., & Sheng, M. (2017) · Kidney & Blood Pressure Research · doi:10.1159/000476017 · Cited by 1,406
A proteomic atlas of senescence-associated secretomes for aging biomarker development
Basisty, N., Kale, A., Jeon, O. H., Kuehnemann, C., Payne, T., Rao, C., Holtz, A., Shah, S., Sharma, V., Ferrucci, L., et al. (2020) · PLOS Biology · doi:10.1371/journal.pbio.3000599 · Cited by 1,348
Cellular senescence promotes adverse effects of chemotherapy and cancer relapse
Demaria, M., O'Leary, M. N., Chang, J., Shao, L., Liu, S., Alimirah, F., Koenig, K., Le, C., Mitin, N., Deal, A. M., et al. (2017) · Cancer Discovery · doi:10.1158/2159-8290.cd-16-0241 · Cited by 1,338
Senescent cells: an emerging target for diseases of ageing
Childs, B. G., Gluscevic, M., Baker, D. J., Laberge, R.-M., Marquess, D., Dananberg, J., & van Deursen, J. M. (2017) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2017.116 · Cited by 1,284
Induction of Apoptosis by Cancer Chemotherapy
Kaufmann, S. H., & Earnshaw, W. C. (2000) · Experimental Cell Research · doi:10.1006/excr.2000.4838 · Cited by 1,266
Senolytics in idiopathic pulmonary fibrosis: Results from a first-in-human, open-label, pilot study
Justice, J. N., Nambiar, A. M., Tchkonia, T., LeBrasseur, N. K., Pascual, R., Hashmi, S. K., Prata, L., Masternak, M. M., Kritchevsky, S. B., Musi, N., et al. (2019) · EBioMedicine · doi:10.1016/j.ebiom.2018.12.052 · Cited by 1,261
Senolytic drugs: from discovery to translation
Kirkland, J. L., & Tchkonia, T. (2020) · Journal of Internal Medicine · doi:10.1111/joim.13141 · Cited by 1,227
Oncogene-induced senescence as an initial barrier in lymphoma development
Braig, M., Lee, S., Loddenkemper, C., Rudolph, C., Peters, A. H. F. M., Schlegelberger, B., Stein, H., Dörken, B., Jenuwein, T., & Schmitt, C. A. (2005) · Nature · doi:10.1038/nature03841 · Cited by 1,220
MTOR regulates the pro-tumorigenic senescence-associated secretory phenotype by promoting IL1A translation
Laberge, R.-M., Sun, Y., Orjalo, A. V., Patil, C. K., Freund, A., Zhou, L., Curran, S. C., Davalos, A. R., Wilson-Edell, K. A., Liu, S., et al. (2015) · Nature Cell Biology · doi:10.1038/ncb3195 · Cited by 1,160
Identification of a novel senolytic agent, navitoclax, targeting the Bcl‐2 family of anti‐apoptotic factors
Zhu, Y., Tchkonia, T., Fuhrmann‐Stroissnigg, H., Dai, H. M., Ling, Y. Y., Stout, M. B., Pirtskhalava, T., Giorgadze, N., Johnson, K. O., Giles, C. B., et al. (2016) · Aging Cell · doi:10.1111/acel.12445 · Cited by 1,148
Hijacking the E3 Ubiquitin Ligase Cereblon to Efficiently Target BRD4
Lu, J., Qian, Y., Altieri, M., Dong, H., Wang, J., Raina, K., Hines, J., Winkler, J. D., Crew, A. P., Coleman, K., et al. (2015) · Chemistry & Biology · doi:10.1016/j.chembiol.2015.05.009 · Cited by 1,140
Senescence-associated reprogramming promotes cancer stemness
Milanovic, M., Fan, D. N. Y., Belenki, D., Däbritz, J. H. M., Zhao, Z., Yu, Y., Dörr, J. R., Dimitrova, L., Lenze, D., Monteiro Barbosa, I. A., et al. (2018) · Nature · doi:10.1038/nature25167 · Cited by 1,131
Senescence in tumours: evidence from mice and humans
Collado, M., & Serrano, M. (2010) · Nature Reviews Cancer · doi:10.1038/nrc2772 · Cited by 1,124
Forging a signature of in vivo senescence
Sharpless, N. E., & Sherr, C. J. (2015) · Nature Reviews Cancer · doi:10.1038/nrc3960 · Cited by 1,104
Senolytic CAR T cells reverse senescence-associated pathologies
Amor, C., Feucht, J., Leibold, J., Ho, Y.-J., Zhu, C., Alonso-Curbelo, D., Mansilla-Soto, J., Boyer, J. A., Li, X., Giavridis, T., et al. (2020) · Nature · doi:10.1038/s41586-020-2403-9 · Cited by 1,098
A Senescence Program Controlled by p53 and p16INK4a Contributes to the Outcome of Cancer Therapy
Schmitt, C. A., Fridman, J. S., Yang, M., Lee, S., Baranov, E., Hoffman, R. M., & Lowe, S. W. (2002) · Cell · doi:10.1016/s0092-8674(02)00734-1 · Cited by 1,050
Directed elimination of senescent cells by inhibition of BCL-W and BCL-XL
Yosef, R., Pilpel, N., Tokarsky-Amiel, R., Biran, A., Ovadya, Y., Cohen, S., Vadai, E., Dassa, L., Shahar, E., Condiotti, R., et al. (2016) · Nature Communications · doi:10.1038/ncomms11190 · Cited by 1,032
Fisetin is a senotherapeutic that extends health and lifespan
Yousefzadeh, M. J., Zhu, Y., McGowan, S. J., Angelini, L., Fuhrmann-Stroissnigg, H., Xu, M., Ling, Y. Y., Melos, K. I., Pirtskhalava, T., Inman, C. L., et al. (2018) · EBioMedicine · doi:10.1016/j.ebiom.2018.09.015 · Cited by 1,032
Cyclin D–CDK4 kinase destabilizes PD-L1 via cullin 3–SPOP to control cancer immune surveillance
Zhang, J., Bu, X., Wang, H., Zhu, Y., Geng, Y., Nihira, N. T., Tan, Y., Ci, Y., Wu, F., Dai, X., et al. (2018) · Nature · doi:10.1038/nature25015 · Cited by 1,013
cGAS is essential for cellular senescence
Yang, H., Wang, H., Ren, J., Chen, Q., & Chen, Z. J. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1705499114 · Cited by 1,009
The rediscovery of platinum-based cancer therapy
Rottenberg, S., Disler, C., & Perego, P. (2020) · Nature reviews. Cancer · doi:10.1038/s41568-020-00308-y · Cited by 993
Regulation of p53 in response to DNA damage
Lakin, N. D., & Jackson, S. P. (1999) · Oncogene · doi:10.1038/sj.onc.1203015 · Cited by 987
The DNA damage response induces inflammation and senescence by inhibiting autophagy of GATA4.
Kang, C., Xu, Q., Martin, T. D., Li, M. Z., Demaria, M., Aron, L., Lu, T., Yankner, B. A., Campisi, J., & Elledge, S. J. (2015) · Science · doi:10.1126/science.aaa5612 · Cited by 982
Unmasking Transcriptional Heterogeneity in Senescent Cells
Hernandez-Segura, A., de Jong, T. V., Melov, S., Guryev, V., Campisi, J., & Demaria, M. (2017) · Current Biology · doi:10.1016/j.cub.2017.07.033 · Cited by 972
An aged immune system drives senescence and ageing of solid organs
Yousefzadeh, M. J., Flores, R. R., Zhu, Y., Schmiechen, Z. C., Brooks, R. W., Trussoni, C. E., Cui, Y., Angelini, L., Lee, K.-A., McGowan, S. J., et al. (2021) · Nature · doi:10.1038/s41586-021-03547-7 · Cited by 972
Unmasking senescence: context-dependent effects of SASP in cancer
Faget, D. V., Ren, Q., & Stewart, S. A. (2019) · Nature Reviews Cancer · doi:10.1038/s41568-019-0156-2 · Cited by 863
PROTAC-induced BET protein degradation as a therapy for castration-resistant prostate cancer
Raina, K., Lu, J., Qian, Y., Altieri, M., Gordon, D., Rossi, A. M. K., Wang, J., Chen, X., Dong, H., Siu, K., et al. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1521738113 · Cited by 852
Telomeric DNA damage is irreparable and causes persistent DNA-damage-response activation
Fumagalli, M., Rossiello, F., Clerici, M., Barozzi, S., Cittaro, D., Kaplunov, J. M., Bucci, G., Dobreva, M., Matti, V., Beausejour, C. M., et al. (2012) · Nature Cell Biology · doi:10.1038/ncb2466 · Cited by 851
Therapy-induced senescence in cancer.
Ewald, J. A., Desotelle, J. A., Wilding, G., & Jarrard, D. F. (2010) · JNCI: Journal of the National Cancer Institute · doi:10.1093/jnci/djq364 · Cited by 824
mTOR regulates MAPKAPK2 translation to control the senescence-associated secretory phenotype
Herranz, N., Gallage, S., Mellone, M., Wuestefeld, T., Klotz, S., Hanley, C. J., Raguz, S., Acosta, J. C., Innes, A. J., Banito, A., et al. (2015) · Nature Cell Biology · doi:10.1038/ncb3225 · Cited by 788
Early Adaptation and Acquired Resistance to CDK4/6 Inhibition in Estrogen Receptor–Positive Breast Cancer
Herrera-Abreu, M. T., Palafox, M., Asghar, U. S., Rivas, M. A., Cutts, R. J., García-Murillas, I., Pearson, A., Guzmán, M., Rodríguez, O., Grueso, J., et al. (2016) · Cancer Research · doi:10.1158/0008-5472.can-15-0728 · Cited by 781
CDK4/6 Inhibition Augments Antitumor Immunity by Enhancing T-cell Activation
Deng, J., Wang, E. S., Jenkins, R. W., Li, S., Dries, R., Yates, K., Chhabra, S., Huang, W., Liu, H., Aref, A. R., et al. (2018) · Cancer Discovery · doi:10.1158/2159-8290.cd-17-0915 · Cited by 770
Non-Cell-Autonomous Tumor Suppression by p53
Lujambio, A., Akkari, L., Simon, J., Grace, D., Tschaharganeh, D. F., Bolden, J. E., Zhao, Z., Thapar, V., Joyce, J. A., Krizhanovsky, V., et al. (2013) · Cell · doi:10.1016/j.cell.2013.03.020 · Cited by 766
Microarray analysis of replicative senescence
Shelton, D. N., Chang, E., Whittier, P. S., Choi, D., & Funk, W. D. (1999) · Current Biology · doi:10.1016/s0960-9822(99)80420-5 · Cited by 764
A senescent cell bystander effect: senescence‐induced senescence
Nelson, G., Wordsworth, J., Wang, C., Jurk, D., Lawless, C., Martin‐Ruiz, C., & von Zglinicki, T. (2012) · Aging Cell · doi:10.1111/j.1474-9726.2012.00795.x · Cited by 755
T-helper-1-cell cytokines drive cancer into senescence
Braumüller, H., Wieder, T., Brenner, E., Aßmann, S., Hahn, M., Alkhaled, M., Schilbach, K., Essmann, F., Kneilling, M., Griessinger, C., et al. (2013) · Nature · doi:10.1038/nature11824 · Cited by 720
The two faces of IL-6 in the tumor microenvironment
Fisher, D. T., Appenheimer, M. M., & Evans, S. S. (2014) · Seminars in Immunology · doi:10.1016/j.smim.2014.01.008 · Cited by 693
Mutant p53 drives metastasis and overcomes growth arrest/senescence in pancreatic cancer
Morton, J. P., Timpson, P., Karim, S. A., Ridgway, R. A., Athineos, D., Doyle, B., Jamieson, N. B., Oien, K. A., Lowy, A. M., Brunton, V. G., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0908428107 · Cited by 657
Cell surface-bound IL-1α is an upstream regulator of the senescence-associated IL-6/IL-8 cytokine network
Orjalo, A. V., Bhaumik, D., Gengler, B. K., Scott, G. K., & Campisi, J. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0905299106 · Cited by 654
The senescence-associated secretory phenotype induces cellular plasticity and tissue regeneration.
Ritschka, B., Storer, M., Mas, A., Heinzmann, F., Ortells, M. C., Morton, J. P., Sansom, O. J., Zender, L., & Keyes, W. M. (2017) · Genes & Development · doi:10.1101/gad.290635.116 · Cited by 650
Plasminogen activator inhibitor-1 is a critical downstream target of p53 in the induction of replicative senescence
Kortlever, R. M., Higgins, P. J., & Bernards, R. (2006) · Nature Cell Biology · doi:10.1038/ncb1448 · Cited by 637
Self-citation
Bora and the Kinase Aurora A Cooperatively Activate the Kinase Plk1 and Control Mitotic Entry
Seki, A., Coppinger, J. A., Jang, C., Yates, J. R., & Fang, G. (2008) · Science · doi:10.1126/science.1157425 · Cited by 622
Distinct Functions of Senescence-Associated Immune Responses in Liver Tumor Surveillance and Tumor Progression
Eggert, T., Wolter, K., Ji, J., Ma, C., Yevsa, T., Klotz, S., Medina-Echeverz, J., Longerich, T., Forgues, M., Reisinger, F., et al. (2016) · Cancer Cell · doi:10.1016/j.ccell.2016.09.003 · Cited by 609
Untitled work
(2003) · PubMed · Cited by 608
Modeling the Therapeutic Efficacy of p53 Restoration in Tumors
Martins, C. P., Brown-Swigart, L., & Evan, G. I. (2006) · Cell · doi:10.1016/j.cell.2006.12.007 · Cited by 600
The dynamic nature of senescence in cancer
Lee, S., & Schmitt, C. A. (2019) · Nature Cell Biology · doi:10.1038/s41556-018-0249-2 · Cited by 588
Elevated serum interleukin-8 is associated with enhanced intratumor neutrophils and reduced clinical benefit of immune-checkpoint inhibitors
Schalper, K. A., Carleton, M. O., Zhou, M., Chen, T., Feng, Y., Huang, S., Walsh, A. M., Baxi, V. A., Pandya, D., Baradet, T. C., et al. (2020) · Nature Medicine · doi:10.1038/s41591-020-0856-x · Cited by 573
Untitled work
(1999) · PubMed · Cited by 546
Synthetic lethal metabolic targeting of cellular senescence in cancer therapy
Dörr, J. R., Yu, Y., Milanovic, M., Beuster, G., Zasada, C., Däbritz, J. H. M., Lisec, J., Lenze, D., Gerhardt, A., Schleicher, K., et al. (2013) · Nature · doi:10.1038/nature12437 · Cited by 541
Microtubule inhibitors: Differentiating tubulin-inhibiting agents based on mechanisms of action, clinical activity, and resistance
Perez, E. A. (2009) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-09-0366 · Cited by 523
NOTCH1 mediates a switch between two distinct secretomes during senescence
Hoare, M., Ito, Y., Kang, T.-W., Weekes, M. P., Matheson, N. J., Patten, D. A., Shetty, S., Parry, A. J., Menon, S., Salama, R., et al. (2016) · Nature Cell Biology · doi:10.1038/ncb3397 · Cited by 522
Immunosenescence: a key player in cancer development
Lian, J., Yue, Y., Yu, W., & Zhang, Y. (2020) · Journal of Hematology & Oncology · doi:10.1186/s13045-020-00986-z · Cited by 510
Senescent Cells in Cancer Therapy: Friends or Foes?
Wang, B., Kohli, J., & Demaria, M. (2020) · Trends in Cancer · doi:10.1016/j.trecan.2020.05.004 · Cited by 508
Tumor Suppressor and Aging Biomarker p16INK4a Induces Cellular Senescence without the Associated Inflammatory Secretory Phenotype
Coppé, J.-P., Rodier, F., Patil, C. K., Freund, A., Desprez, P.-Y., & Campisi, J. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.257071 · Cited by 506
P53 and radiation responses
Fei, P., & El‐Deiry, W. S. (2003) · Oncogene · doi:10.1038/sj.onc.1206677 · Cited by 503
Senescent Human Fibroblasts Increase the Early Growth of Xenograft Tumors via Matrix Metalloproteinase Secretion
Liu, D., & Hornsby, P. J. (2007) · Cancer Research · doi:10.1158/0008-5472.can-06-3452 · Cited by 499
Senescent cell clearance by the immune system: Emerging therapeutic opportunities
Prata, L. G. P. L., Ovsyannikova, I. G., Tchkonia, T., & Kirkland, J. L. (2018) · Seminars in Immunology · doi:10.1016/j.smim.2019.04.003 · Cited by 497
Stromal senescence establishes an immunosuppressive microenvironment that drives tumorigenesis
Ruhland, M. K., Loza, A. J., Capietto, A.-H., Luo, X., Knolhoff, B. L., Flanagan, K. C., Belt, B. A., Alspach, E., Leahy, K., Luo, J., et al. (2016) · Nature Communications · doi:10.1038/ncomms11762 · Cited by 496
Targeting CDK4/6 in patients with cancer
Hamilton, E. P., & Infante, J. R. (2016) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2016.03.002 · Cited by 495
Synthetic Lethality and Cancer Therapy: Lessons Learned from the Development of PARP Inhibitors
Lord, C. J., Tutt, A. N. J., & Ashworth, A. (2014) · Annual Review of Medicine · doi:10.1146/annurev-med-050913-022545 · Cited by 493
Dose-dependent oncogene-induced senescence in vivo and its evasion during mammary tumorigenesis
Sarkisian, C. J., Keister, B. A., Stairs, D. B., Boxer, R. B., Moody, S. E., & Chodosh, L. A. (2007) · Nature Cell Biology · doi:10.1038/ncb1567 · Cited by 490
Senescence-Associated Exosome Release from Human Prostate Cancer Cells
Lehmann, B. D., Paine, M. S., Brooks, A. M., McCubrey, J. A., Renegar, R. H., Wang, R., & Terrian, D. M. (2008) · Cancer Research · doi:10.1158/0008-5472.can-07-6538 · Cited by 464
NF-κB inhibition delays DNA damage–induced senescence and aging in mice
Tilstra, J. S., Robinson, A. R., Wang, J., Gregg, S. Q., Clauson, C. L., Reay, D. P., Nasto, L. A., St Croix, C. M., Usas, A., Vo, N., et al. (2012) · Journal of Clinical Investigation · doi:10.1172/jci45785 · Cited by 462
ATM-ATR–dependent up-regulation of DNAM-1 and NKG2D ligands on multiple myeloma cells by therapeutic agents results in enhanced NK-cell susceptibility and is associated with a senescent phenotype
Soriani, A., Zingoni, A., Cerboni, C., Iannitto, M. L., Ricciardi, M. R., Di Gialleonardo, V., Cippitelli, M., Fionda, C., Petrucci, M. T., Guarini, A., et al. (2009) · Blood · doi:10.1182/blood-2008-08-173914 · Cited by 460
Defined p16High Senescent Cell Types Are Indispensable for Mouse Healthspan
Grosse, L., Wagner, N., Emelyanov, A., Molina, C., Lacas-Gervais, S., Wagner, K.-D., & Bulavin, D. V. (2020) · Cell Metabolism · doi:10.1016/j.cmet.2020.05.002 · Cited by 460
p53: Guardian of the Genome and Policeman of the Oncogenes
Efeyan, A., & Serrano, M. (2007) · Cell Cycle · doi:10.4161/cc.6.9.4211 · Cited by 451
Pro-senescence therapy for cancer treatment
Nardella, C., Clohessy, J. G., Alimonti, A., & Pandolfi, P. P. (2011) · Nature Reviews Cancer · doi:10.1038/nrc3057 · Cited by 437
High systemic and tumor-associated IL-8 correlates with reduced clinical benefit of PD-L1 blockade
Yuen, K. C. Y., Liu, L.-F., Gupta, V., Madireddi, S., Keerthivasan, S., Li, C., Rishipathak, D., Williams, P. T., Kadel, E. E., Koeppen, H., et al. (2020) · Nature Medicine · doi:10.1038/s41591-020-0860-1 · Cited by 436
Escape from Therapy-Induced Accelerated Cellular Senescence in p53-Null Lung Cancer Cells and in Human Lung Cancers
Roberson, R. S., Kussick, S. J., Vallieres, E., Chen, S.-Y. J., & Wu, D. Y. (2005) · Cancer Research · doi:10.1158/0008-5472.can-04-1270 · Cited by 428
Inducing and exploiting vulnerabilities for the treatment of liver cancer
Wang, C., Vegna, S., Jin, H., Benedict, B., Lieftink, C., Ramirez, C., de Oliveira, R. L., Morris, B., Gadiot, J., Wang, W., et al. (2019) · Nature · doi:10.1038/s41586-019-1607-3 · Cited by 427
Self-citation
Senescence-Induced Vascular Remodeling Creates Therapeutic Vulnerabilities in Pancreas Cancer
Ruscetti, M., Morris, J. P., Mezzadra, R., Russell, J., Leibold, J., Romesser, P. B., Simon, J., Kulick, A., Ho, Y.-J., Fennell, M., et al. (2020) · Cell · doi:10.1016/j.cell.2020.03.008 · Cited by 424
Enhancing Chemotherapy Efficacy in Pten-Deficient Prostate Tumors by Activating the Senescence-Associated Antitumor Immunity
Toso, A., Revandkar, A., Di Mitri, D., Guccini, I., Proietti, M., Sarti, M., Pinton, S., Zhang, J., Kalathur, M., Civenni, G., et al. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.08.044 · Cited by 418
Cellular senescence is an important mechanism of tumor regression upon c-Myc inactivation
Wu, C.-H., van Riggelen, J., Yetil, A., Fan, A. C., Bachireddy, P., & Felsher, D. W. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0701953104 · Cited by 417
NK cell–mediated cytotoxicity contributes to tumor control by a cytostatic drug combination
Ruscetti, M., Leibold, J., Bott, M. J., Fennell, M., Kulick, A., Salgado, N. R., Chen, C.-C., Ho, Y.-J., Sanchez-Rivera, F. J., Feucht, J., et al. (2018) · Science · doi:10.1126/science.aas9090 · Cited by 415
p53-dependent chemokine production by senescent tumor cells supports NKG2D-dependent tumor elimination by natural killer cells
Iannello, A., Thompson, T. W., Ardolino, M., Lowe, S. W., & Raulet, D. H. (2013) · Journal of Experimental Medicine · doi:10.1084/jem.20130783 · Cited by 414
Small extracellular vesicles secreted from senescent cells promote cancer cell proliferation through EphA2
Takasugi, M., Okada, R., Takahashi, A., Virya Chen, D., Watanabe, S., & Hara, E. (2017) · Nature Communications · doi:10.1038/ncomms15728 · Cited by 410
Mitochondrial Dysfunction Contributes to Oncogene-Induced Senescence
Moiseeva, O., Bourdeau, V., Roux, A., Deschênes-Simard, X., & Ferbeyre, G. (2009) · Molecular and Cellular Biology · doi:10.1128/mcb.01868-08 · Cited by 408
Senescence-associated inflammatory responses: aging and cancer perspectives
Lasry, A., & Ben-Neriah, Y. (2015) · Trends in Immunology · doi:10.1016/j.it.2015.02.009 · Cited by 408
Mitogen‐activated protein kinase p38 defines the common senescence‐signalling pathway
Iwasa, H., Han, J., & Ishikawa, F. (2003) · Genes to Cells · doi:10.1046/j.1365-2443.2003.00620.x · Cited by 407
p16(Ink4a) and senescence-associated β-galactosidase can be induced in macrophages as part of a reversible response to physiological stimuli
Hall, B. M., Balan, V., Gleiberman, A. S., Strom, E., Krasnov, P., Virtuoso, L. P., Rydkina, E., Vujcic, S., Balan, K., Gitlin, I. I., et al. (2017) · Aging · doi:10.18632/aging.101268 · Cited by 407
The senescence-associated secretome as an indicator of age and medical risk
Schafer, M. J., Zhang, X., Kumar, A., Atkinson, E. J., Zhu, Y., Jachim, S., Mazula, D. L., Brown, A. K., Berning, M., Aversa, Z., et al. (2020) · JCI Insight · doi:10.1172/jci.insight.133668 · Cited by 401
Phase II Trial of the CDK4 Inhibitor PD0332991 in Patients With Advanced CDK4 -Amplified Well-Differentiated or Dedifferentiated Liposarcoma
Dickson, M. A., Tap, W. D., Keohan, M. L., D'Angelo, S. P., Gounder, M. M., Antonescu, C. R., Landa, J., Qin, L.-X., Rathbone, D. D., Condy, M. M., et al. (2013) · Journal of Clinical Oncology · doi:10.1200/jco.2012.46.5476 · Cited by 399
Discovery of RG7112: a small-molecule MDM2 inhibitor in clinical development
Vu, B., Wovkulich, P., Pizzolato, G., Lovey, A., Ding, Q., Jiang, N., Liu, J.-J., Zhao, C., Glenn, K., Wen, Y., et al. (2013) · ACS Medicinal Chemistry Letters · doi:10.1021/ml4000657 · Cited by 395
Dual CDK4/CDK6 Inhibition Induces Cell-Cycle Arrest and Senescence in Neuroblastoma
Rader, J., Russell, M. R., Hart, L. S., Nakazawa, M. S., Belcastro, L. T., Martinez, D., Li, Y., Carpenter, E. L., Attiyeh, E. F., Diskin, S. J., et al. (2013) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-13-1675 · Cited by 394
Combine and conquer: challenges for targeted therapy combinations in early phase trials
Lopez, J. S., & Banerji, U. (2017) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2016.96 · Cited by 394
Tumour-infiltrating Gr-1+ myeloid cells antagonize senescence in cancer
Di Mitri, D., Toso, A., Chen, J. J., Sarti, M., Pinton, S., Jost, T. R., D’Antuono, R., Montani, E., Garcia-Escudero, R., Guccini, I., et al. (2014) · Nature · doi:10.1038/nature13638 · Cited by 388
Role of p53 and p21waf1/cip1 in senescence-like terminal proliferation arrest induced in human tumor cells by chemotherapeutic drugs
Chang, B.-D., Xuan, Y., Broude, E. V., Zhu, H., Schott, B., Fang, J., & Roninson, I. B. (1999) · Oncogene · doi:10.1038/sj.onc.1203078 · Cited by 387
Identification and characterization of Cardiac Glycosides as senolytic compounds
Triana-Martínez, F., Picallos-Rabina, P., Da Silva-Álvarez, S., Pietrocola, F., Llanos, S., Rodilla, V., Soprano, E., Pedrosa, P., Ferreirós, A., Barradas, M., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-12888-x · Cited by 384
Molecular mechanisms of resistance to CDK4/6 inhibitors in breast cancer: A review
Pandey, K., An, H. J., Kim, S., Lee, S. A., Kim, S., Lim, S. M., Kim, G. M., Sohn, J., & Moon, Y. W. (2018) · International Journal of Cancer · doi:10.1002/ijc.32020 · Cited by 376
A novel type of cellular senescence that can be enhanced in mouse models and human tumor xenografts to suppress prostate tumorigenesis
Alimonti, A., Nardella, C., Chen, Z., Clohessy, J. G., Carracedo, A., Trotman, L. C., Cheng, K., Varmeh, S., Kozma, S. C., Thomas, G., et al. (2010) · Journal of Clinical Investigation · doi:10.1172/jci40535 · Cited by 374
Cardiac glycosides are broad-spectrum senolytics
Guerrero, A., Herranz, N., Sun, B., Wagner, V., Gallage, S., Guiho, R., Wolter, K., Pombo, J., Irvine, E. E., Innes, A. J., et al. (2019) · Nature Metabolism · doi:10.1038/s42255-019-0122-z · Cited by 359
Virus-induced senescence is a driver and therapeutic target in COVID-19
Lee, S., Yu, Y., Trimpert, J., Benthani, F., Mairhofer, M., Richter-Pechanska, P., Wyler, E., Belenki, D., Kaltenbrunner, S., Pammer, M., et al. (2021) · Nature · doi:10.1038/s41586-021-03995-1 · Cited by 350
NKG2D ligands mediate immunosurveillance of senescent cells
Sagiv, A., Burton, D. G. A., Moshayev, Z., Vadai, E., Wensveen, F., Ben-Dor, S., Golani, O., Polic, B., & Krizhanovsky, V. (2016) · Aging · doi:10.18632/aging.100897 · Cited by 345
The chemokine growth-regulated oncogene 1 (Gro-1) links RAS signaling to the senescence of stromal fibroblasts and ovarian tumorigenesis
Yang, G., Rosen, D. G., Zhang, Z., Bast, R. C., Mills, G. B., Colacino, J. A., Mercado-Uribe, I., & Liu, J. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0605752103 · Cited by 341
A versatile drug delivery system targeting senescent cells
Muñoz‐Espín, D., Rovira, M., Galiana, I., Giménez, C., Lozano‐Torres, B., Paez‐Ribes, M., Llanos, S., Chaib, S., Muñoz‐Martín, M., Ucero, A. C., et al. (2018) · EMBO Molecular Medicine · doi:10.15252/emmm.201809355 · Cited by 339
Mechanisms of cellular senescence in human and mouse cells.
Itahana, K., Campisi, J., & Dimri, G. P. (2004) · Biogerontology · doi:10.1023/b:bgen.0000017682.96395.10 · Cited by 338
Mechanism of Human Telomerase Inhibition by BIBR1532, a Synthetic, Non-nucleosidic Drug Candidate
Pascolo, E., Wenz, C., Lingner, J., Hauel, N. H., Priepke, H. W. M., Kauffmann, I., Garin‐Chesa, P., Rettig, W. J., Damm, K., & Schnapp, A. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m201266200 · Cited by 336
An Acquired Vulnerability of Drug-Resistant Melanoma with Therapeutic Potential
Wang, L., de Oliveira, R. L., Huijberts, S. C. F. A., Bosdriesz, E., Pencheva, N., Brunen, D., Bosma, A. R., Song, J., Zevenhoven, J., Vries, G. T. L.-D., et al. (2018) · Cell · doi:10.1016/j.cell.2018.04.012 · Cited by 334
Self-citation
Cancer-associated fibroblasts induce epithelial–mesenchymal transition of bladder cancer cells through paracrine IL-6 signalling
Goulet, C. R., Champagne, A., Bernard, G., Vandal, D., Chabaud, S., Pouliot, F., & Bolduc, S. (2019) · BMC Cancer · doi:10.1186/s12885-019-5353-6 · Cited by 333
Impact of senescence-associated secretory phenotype and its potential as a therapeutic target for senescence-associated diseases
Watanabe, S., Kawamoto, S., Ohtani, N., & Hara, E. (2017) · Cancer Science · doi:10.1111/cas.13184 · Cited by 321
The unfolded protein response and cellular senescence. A Review in the Theme: Cellular Mechanisms of Endoplasmic Reticulum Stress Signaling in Health and Disease
Pluquet, O., Pourtier, A., & Abbadie, C. (2015) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00334.2014 · Cited by 305
Galacto‐conjugation of Navitoclax as an efficient strategy to increase senolytic specificity and reduce platelet toxicity
González‐Gualda, E., Pàez‐Ribes, M., Lozano‐Torres, B., Macias, D., Wilson, J. R., González‐López, C., Ou, H., Mirón‐Barroso, S., Zhang, Z., Lérida‐Viso, A., et al. (2020) · Aging Cell · doi:10.1111/acel.13142 · Cited by 303
Senescence-Associated Secretory Phenotypes Reveal Cell-Nonautonomous Functions of Oncogenic RAS and the p53 Tumor Suppressor
Coppé, J.-P., Patil, C. K., Rodier, F., Sun, Y., Muñoz, D. P., Goldstein, J., Nelson, P. S., Desprez, P.-Y., & Campisi, J. (2008) · PLoS Biology · doi:10.1371/journal.pbio.0060301 · Cited by 302
Accelerated senescence: An emerging role in tumor cell response to chemotherapy and radiation
Gewirtz, D. A., Holt, S. E., & Elmore, L. W. (2008) · Biochemical Pharmacology · doi:10.1016/j.bcp.2008.06.024 · Cited by 301
Selective CDK4/6 inhibition with tumor responses by PD0332991 in patients with mantle cell lymphoma
Leonard, J. P., LaCasce, A. S., Smith, M. R., Noy, A., Chirieac, L. R., Rodig, S. J., Yu, J. Q., Vallabhajosula, S., Schoder, H., English, P., et al. (2012) · Blood · doi:10.1182/blood-2011-10-388298 · Cited by 299
Therapy-Induced Senescence: An “Old” Friend Becomes the Enemy
Saleh, T., Bloukh, S., Carpenter, V. J., Alwohoush, E., Bakeer, J., Darwish, S., Azab, B., & Gewirtz, D. A. (2020) · Cancers · doi:10.3390/cancers12040822 · Cited by 295
Targeting senescent cells in translational medicine
Paez‐Ribes, M., González‐Gualda, E., Doherty, G. J., & Muñoz‐Espín, D. (2019) · EMBO Molecular Medicine · doi:10.15252/emmm.201810234 · Cited by 293
Pharmacologic modulation of RNA splicing enhances anti-tumor immunity
Lu, S. X., Neef, E. D., Thomas, J. D., Sabio, E. Y., Rousseau, B., Gigoux, M., Knorr, D. A., Greenbaum, B. D., Elhanati, Y., Hogg, S. J., et al. (2021) · Cell · doi:10.1016/j.cell.2021.05.038 · Cited by 286
Using proteolysis-targeting chimera technology to reduce navitoclax platelet toxicity and improve its senolytic activity
He, Y., Zhang, X., Chang, J., Kim, H.-N., Zhang, P., Wang, Y., Khan, S., Liu, X., Zhang, X., Lv, D., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-15838-0 · Cited by 280
Identification of senescent cell surface targetable protein DPP4
Kim, K. M., Noh, J. H., Bodogai, M., Martindale, J. L., Yang, X., Indig, F. E., Basu, S. K., Ohnuma, K., Morimoto, C., Johnson, P. F., et al. (2017) · Genes & Development · doi:10.1101/gad.302570.117 · Cited by 270
Reversal of Senescence in Mouse Fibroblasts through Lentiviral Suppression of p53
Dirac, A. M. G., & Bernards, R. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.c300023200 · Cited by 265
Self-citation
Host tissue determinants of tumour immunity
Salmon, H., Remark, R., Gnjatic, S., & Mérad, M. (2019) · Nature reviews. Cancer · doi:10.1038/s41568-019-0125-9 · Cited by 263
Serum interleukin-6 and C-reactive protein are associated with survival in melanoma patients receiving immune checkpoint inhibition
Laino, A. S., Woods, D. M., Vassallo, M., Qian, X., Tang, H., Wind‐Rotolo, M., & Weber, J. S. (2020) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2020-000842 · Cited by 259
Cdk2 suppresses cellular senescence induced by the c-myc oncogene
Campaner, S., Doni, M., Hydbring, P., Verrecchia, A., Bianchi, L., Sardella, D., Schleker, T., Perna, D., Tronnersjö, S., Murga, M., et al. (2009) · Nature Cell Biology · doi:10.1038/ncb2004 · Cited by 258
Characterization of novel markers of senescence and their prognostic potential in cancer
Althubiti, M., Lezina, L., Carrera, S., Jukes-Jones, R., Giblett, S. M., Antonov, A., Barlev, N., Saldanha, G. S., Pritchard, C. A., Cain, K., et al. (2014) · Cell Death & Disease · doi:10.1038/cddis.2014.489 · Cited by 256
Cause and Consequence of Cancer/Testis Antigen Activation in Cancer
Whitehurst, A. W. (2013) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-011112-140326 · Cited by 255
Genomic Aberrations that Activate D-type Cyclins Are Associated with Enhanced Sensitivity to the CDK4 and CDK6 Inhibitor Abemaciclib
Gong, X., Litchfield, L. M., Webster, Y., Chio, L.-C., Wong, S. S., Stewart, T. R., Dowless, M. S., Dempsey, J. A., Zeng, Y. A., Torres, R., et al. (2017) · Cancer Cell · doi:10.1016/j.ccell.2017.11.006 · Cited by 246
Small molecule compounds that induce cellular senescence.
Petrova, N. V., Velichko, A. K., Razin, S. V., & Kantidze, O. L. (2016) · Aging Cell · doi:10.1111/acel.12518 · Cited by 240
A Senescence-Inflammatory Switch from Cancer-Inhibitory to Cancer-Promoting Mechanism
Pribluda, A., Elyada, E., Wiener, Z., Hamza, H., Goldstein, R. E., Biton, M., Burstain, I., Morgenstern, Y., Brachya, G., Billauer, H., et al. (2013) · Cancer Cell · doi:10.1016/j.ccr.2013.06.005 · Cited by 239
Senolytic therapies for healthy longevity.
van Deursen, J. M. (2019) · Science · doi:10.1126/science.aaw1299 · Cited by 237
Senescence and Cancer: A Review of Clinical Implications of Senescence and Senotherapies
Wyld, L., Bellantuono, I., Tchkonia, T., Morgan, J., Turner, O., Foss, F., George, J., Danson, S., & Kirkland, J. L. (2020) · Cancers · doi:10.3390/cancers12082134 · Cited by 235
Exploiting interconnected synthetic lethal interactions between PARP inhibition and cancer cell reversible senescence
Fleury, H., Malaquin, N., Tu, V., Gilbert, S., Martinez, A., Olivier, M.-A., Sauriol, S. A., Communal, L., Leclerc-Desaulniers, K., Carmona, E., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-10460-1 · Cited by 228
The differential impact of p16INK4a or p19ARF deficiency on cell growth and tumorigenesis
Sharpless, N. E., Ramsey, M. R., Balasubramanian, P., Castrillon, D. H., & DePinho, R. A. (2004) · Oncogene · doi:10.1038/sj.onc.1207074 · Cited by 224
High-Throughput Functional Genetic and Compound Screens Identify Targets for Senescence Induction in Cancer
Wang, L., Leite de Oliveira, R., Wang, C., Fernandes Neto, J. M., Mainardi, S., Evers, B., Lieftink, C., Morris, B., Jochems, F., Willemsen, L., et al. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.09.085 · Cited by 224
Self-citation
Two-Step Senescence-Focused Cancer Therapies
Sieben, C. J., Sturmlechner, I., van de Sluis, B., & van Deursen, J. M. (2018) · Trends in Cell Biology · doi:10.1016/j.tcb.2018.04.006 · Cited by 222
CDK inhibitors (p16/p19/p21) induce senescence and autophagy in cancer-associated fibroblasts, “fueling” tumor growth via paracrine interactions, without an increase in neo-angiogenesis
Capparelli, C., Chiavarina, B., Whitaker-Menezes, D., Pestell, T. G., Pestell, R. G., Hulit, J., Andò, S., Howell, A., Martinez-Outschoorn, U. E., Sotgia, F., et al. (2012) · Cell Cycle · doi:10.4161/cc.21884 · Cited by 221
Therapeutic Efficacy of ABT-737, a Selective Inhibitor of BCL-2, in Small Cell Lung Cancer
Hann, C. L., Daniel, V. C., Sugar, E. A., Dobromilskaya, I., Murphy, S. C., Cope, L., Lin, X., Hierman, J. S., Wilburn, D. L., Watkins, D. N., et al. (2008) · Cancer Research · doi:10.1158/0008-5472.can-07-5031 · Cited by 213
Mechanisms of action of, and modes of resistance to, alkylating agents used in the treatment of haematological malignancies
Hall, A. G., & Tilby, M. J. (1992) · Blood Reviews · doi:10.1016/0268-960x(92)90028-o · Cited by 210
A BET family protein degrader provokes senolysis by targeting NHEJ and autophagy in senescent cells
Wakita, M., Takahashi, A., Sano, O., Loo, T. M., Imai, Y., Narukawa, M., Iwata, H., Matsudaira, T., Kawamoto, S., Ohtani, N., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-15719-6 · Cited by 206
Wnt/β-Catenin Signaling Induces the Aging of Mesenchymal Stem Cells through the DNA Damage Response and the p53/p21 Pathway
Zhang, D., Wang, H., & Tan, Y. (2011) · PLoS ONE · doi:10.1371/journal.pone.0021397 · Cited by 201
The Cancer SENESCopedia: A delineation of cancer cell senescence
Jochems, F., Thijssen, B., De Conti, G., Jansen, R., Pogacar, Z., Groot, K., Wang, L., Schepers, A., Wang, C., Jin, H., et al. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.109441 · Cited by 201
Self-citation
A phase 2 study of the BH3 mimetic BCL2 inhibitor navitoclax (ABT-263) with or without rituximab, in previously untreated B-cell chronic lymphocytic leukemia
Kipps, T. J., Eradat, H. A., Grosicki, S., Catalano, J. V., Cosolo, W., Dyagil, I., Yalamanchili, S., Chai, A., Sahasranaman, S., Punnoose, E. A., et al. (2015) · Leukemia & lymphoma/Leukemia and lymphoma · doi:10.3109/10428194.2015.1030638 · Cited by 196
Deregulated E2F Activity Induces Hyperplasia and Senescence-Like Features in the Mouse Pituitary Gland
Denchi, E. L., Attwooll, C., Pasini, D., & Helin, K. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.7.2660-2672.2005 · Cited by 195
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McCartney, A., Migliaccio, I., Bonechi, M., Biagioni, C., Romagnoli, D., Luca, F. D., Galardi, F., Risi, E., Santo, I. D., Benelli, M., et al. (2019) · Frontiers in Oncology · doi:10.3389/fonc.2019.00666 · Cited by 195
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Omori, S., Wang, T.-W., Johmura, Y., Kanai, T., Nakano, Y., Kido, T., Susaki, E. A., Nakajima, T., Shichino, S., Ueha, S., et al. (2020) · Cell Metabolism · doi:10.1016/j.cmet.2020.09.006 · Cited by 194
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Saleh, T., Carpenter, V. J., Tyutyunyk‐Massey, L., Murray, G., Leverson, J. D., Souers, A. J., Alotaibi, M. R., Faber, A. C., Reed, J., Harada, H., et al. (2020) · Molecular Oncology · doi:10.1002/1878-0261.12761 · Cited by 190
Persistent mTORC1 signaling in cell senescence results from defects in amino acid and growth factor sensing
Carroll, B., Nelson, G., Rabanal‐Ruiz, Y., Kucheryavenko, O., Dunhill-Turner, N. A., Chesterman, C. C., Zahari, Q., Zhang, T., Conduit, S. E., Mitchell, C. A., et al. (2017) · The Journal of Cell Biology · doi:10.1083/jcb.201610113 · Cited by 188
An OFF–ON Two-Photon Fluorescent Probe for Tracking Cell Senescence in Vivo
Lozano‐Torres, B., Galiana, I., Rovira, M., Garrido, E. M. N., Chaib, S., Bernardos, A., Muñoz‐Espín, D., Serrano, M., Martínez‐Máñez, R., & Sancenón, F. (2017) · Journal of the American Chemical Society · doi:10.1021/jacs.7b04985 · Cited by 185
A Comparative Study of Two Regimens of Combination Chemotherapy in Acute Leukemia
Frei, E., Holland, J. F., Schneiderman, M. A., Pinkel, D. P., SELKIRK, G., Freireich, E. J., Silver, R. T., Gold, G. L., & Regelson, W. (1958) · Blood · doi:10.1182/blood.v13.12.1126.1126 · Cited by 182
PTEN status switches cell fate between premature senescence and apoptosis in glioma exposed to ionizing radiation
Lee, J.-J., Kim, B. C., Park, M.-J., Lee, Y., Kim, Y.-N., Lee, B. L., & Js, L. (2010) · Cell Death and Differentiation · doi:10.1038/cdd.2010.139 · Cited by 179
Oxylipin biosynthesis reinforces cellular senescence and allows detection of senolysis
Wiley, C. D., Sharma, R., Davis, S. S., Lopez-Dominguez, J. A., Mitchell, K. P., Wiley, S., Alimirah, F., Kim, D. E., Payne, T., Rosko, A., et al. (2021) · Cell Metabolism · doi:10.1016/j.cmet.2021.03.008 · Cited by 173
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Canavese, M., Santo, L., & Raje, N. S. (2012) · Cancer Biology & Therapy · doi:10.4161/cbt.19589 · Cited by 162
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Muñoz, D. P., Yannone, S. M., Daemen, A., Sun, Y., Vakar-Lopez, F., Kawahara, M., Freund, A. M., Rodier, F., Wu, J. D., Desprez, P.-Y., et al. (2019) · JCI Insight · doi:10.1172/jci.insight.124716 · Cited by 162
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Ionizing Radiation-Induced Cellular Senescence in Normal, Non-transformed Cells and the Involved DNA Damage Response: A Mini Review
Li, M., You, L., Xue, J., & Lü, Y. (2018) · Frontiers in Pharmacology · doi:10.3389/fphar.2018.00522 · Cited by 153
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Teo, Y. V., Rattanavirotkul, N., Olova, N., Salzano, A., Quintanilla, A., Tarrats, N., Kiourtis, C., Müller, M., Green, A. R., Adams, P. D., et al. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.03.104 · Cited by 149
Derepression of hTERT gene expression promotes escape from oncogene-induced cellular senescence
Patel, P. L., Suram, A., Mirani, N., Bischof, O., & Herbig, U. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1602379113 · Cited by 142
Induction of p53-Dependent Senescence by the MDM2 Antagonist Nutlin-3a in Mouse Cells of Fibroblast Origin
Efeyan, A., Ortega-Molina, A., Velasco-Miguel, S., Herranz, D., Vassilev, L. T., & Serrano, M. (2007) · Cancer Research · doi:10.1158/0008-5472.can-07-0200 · Cited by 140
Histone Modifications in Senescence-Associated Resistance to Apoptosis by Oxidative Stress
Sanders, Y. Y., Liu, H., Zhang, X., Hecker, L., Bernard, K., Desai, L., Liu, G., & Thannickal, V. J. (2013) · Redox Biology · doi:10.1016/j.redox.2012.11.004 · Cited by 138
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Brenner, E., Schörg, B. F., Ahmetlić, F., Wieder, T., Hilke, F. J., Simon, N., Schroeder, C., Demidov, G. M., Riedel, T., Fehrenbacher, B., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-14987-6 · Cited by 136
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Pandey, K., Park, N., Park, K., Hur, J., Cho, Y. B., Kang, M., An, H., Kim, S., Hwang, S., & Moon, Y. W. (2020) · Cancers · doi:10.3390/cancers12123566 · Cited by 136
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Freeman‐Cook, K. D., Hoffman, R. L., Behenna, D. C., Boras, B. W., Carelli, J. D., Diehl, W. C., Ferre, R. A., He, Y.-A., Hui, A., Huang, B., et al. (2021) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.1c00159 · Cited by 133

Research works printed but not linked: 1

Ekpenyong-Akiba, A. E., Poblocka, M. & Macip, S. In Senolytics in Disease, Ageing and Longevity (Springer, 2020).

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See all 867

Authors: Wang, L., Lankhorst, L., & Bernards, R.
Affiliations: The Netherlands Cancer Institute (NL)
Utrecht University (NL)
Corresponding author: Bernards, René
ORCID: Wang, Liqin
Lankhorst, Lina
Bernards, René
Venue: Nature Reviews Cancer
Publisher: Springer Science and Business Media LLC
Published: 2022-03-03
Volume: 22
Issue: 6
Pages: 340-355
ISSN: 1474-175X (ISSN-L)
1474-1768
DOI: 10.1038/s41568-022-00450-9
OpenAlex: W4221091893
Cited by: 867
References: 265
Citations by year: 2026: 161 · 2025: 237 · 2024: 254 · 2023: 141 · 2022: 73
FWCI: 24.68
Type: journal article
Language: en
Open access: closed
Licence: www.springernature.com/gp/researchers/text-and-data-mining (tdm)
www.springernature.com/gp/researchers/text-and-data-mining (vor)
Locations: Nature reviews. Cancer (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
Keywords: cellular senescence, senolysis, senolytic therapy
MeSH terms: Cell Cycle, Humans, Neoplasms, Cellular Senescence

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Exploiting senescence for the treatment of cancer

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