Translational approaches targeting the p53 pathway for anti‐cancer therapy
Open accessAbstract
The p53 tumour suppressor blocks cancer development by triggering apoptosis or cellular senescence in response to oncogenic stress or DNA damage. Consequently, the p53 signalling pathway is virtually always inactivated in human cancer cells. This unifying feature has commenced tremendous efforts to develop p53‐based anti‐cancer therapies. Different strategies exist that are adapted to the mechanisms of p53 inactivation. In p53‐mutated tumours, delivery of wild‐type p53 by adenovirus‐based gene therapy is now practised in China. Also, remarkable progress has been made in the development of p53‐binding drugs that can rescue and reactivate the function of mutant or misfolded p53. Other biologic approaches include the development of oncolytic viruses that are designed to specifically replicate in and kill p53‐defective cells. Inactivation of wt‐p53 frequently results from dysregulation of MDM2, an E3 ligase that regulates p53 levels. Small‐molecule drugs that inhibit the interaction of MDM2 and p53 and block p53 degradation are currently tested in clinical trials. This survey highlights the recent developments that attempt to modulate the function of p53 and outlines strategies that are being investigated for pharmacological intervention in the p53 pathway.
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PXN822 binds the p53-binding pocket of Mdm2 and disrupts a preformed p53/Mdm2 complex.
“PXN822 binds to the p53-binding pocket of Mdm2 and disrupts a preformed p53/Mdm2 complex 7,8”
From Mdm2 inhibitors synergize with topoisomerase II inhibitors to induce p53-independent pancreatic cancer cell death (2013) · cites this paper as [8]
Inhibitors of Mdm2 have entered clinical trials.
“Beyond these strategies, inhibitors of Mdm2 have already entered clinical trials, 7,8”
From Mdm2 inhibitors synergize with topoisomerase II inhibitors to induce p53-independent pancreatic cancer cell death (2013) · cites this paper as [8]
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Erratum: PRIMA-1Met induces mitochondrial apoptosis through activation of caspase-2
Shen, J., Vakifahmetoglu, H., Stridh, H., Zhivotovsky, B., & Wiman, K. G. (2016) · Oncogene · doi:10.1038/onc.2016.210 · Cited by 55 · see citing works
RetractedPRIMA-1MET induces mitochondrial apoptosis through activation of caspase-2
Shen, J., Vakifahmetoglu, H., Stridh, H., Zhivotovsky, B., & Wiman, K. G. (2008) · Oncogene · doi:10.1038/onc.2008.249 · Cited by 52 · see citing works
RetractedIn 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 · see citing works
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 · see citing works
Structure of the MDM2 Oncoprotein Bound to the p53 Tumor Suppressor Transactivation Domain
Kussie, P. H., Gorina, S., Marechal, V., Elenbaas, B., Moreau, J., Levine, A. J., & Pavletich, N. P. (1996) · Science · doi:10.1126/science.274.5289.948 · Cited by 2,206 · see citing works
Yang, A., Kaghad, M., Wang, Y., Gillett, E. S., Fleming, M. D., Dötsch, V., Andrews, N. C., Caput, D., & McKeon, F. (1998) · Molecular Cell · doi:10.1016/s1097-2765(00)80275-0 · Cited by 2,086 · see citing works
The p53 pathway: positive and negative feedback loops
Harris, S. L., & Levine, A. J. (2005) · Oncogene · doi:10.1038/sj.onc.1208615 · Cited by 1,967 · see citing works
Amplification of a gene encoding a p53-associated protein in human sarcomas
Oliner, J. D., Kinzler, K. W., Meltzer, P. S., George, D. L., & Vogelstein, B. (1992) · Nature · doi:10.1038/358080a0 · Cited by 1,949 · see citing works
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 · see citing works
An Adenovirus Mutant That Replicates Selectively in p53- Deficient Human Tumor Cells
Bischoff, J. R., Kirn, D. H., Williams, A., Heise, C. C., Horn, S. T., Muna, M., Ng, L., Nye, J. A., Sampson-Johannes, A., Fattaey, A., et al. (1996) · Science · doi:10.1126/science.274.5286.373 · Cited by 1,753 · see citing works
Kaghad, M., Bonnet, H., Yang, A., Créancier, L., Biscan, J.-C., Valent, A., Minty, A. J., Chalon, P., Lélias, J.-M., Dumont, X., et al. (1997) · Cell · doi:10.1016/s0092-8674(00)80540-1 · Cited by 1,630 · see citing works
Petitjean, A., Mathe, E., Kato, S., Ishioka, C., Tavtigian, S. V., Hainaut, P., & Olivier, M. (2007) · Human Mutation · doi:10.1002/humu.20495 · Cited by 1,598 · cited 2× · see citing works
“The Y220C mutation, which is among the 10 most frequent p53 mutations (Petitjean et al., 2007), destabilizes the p53 protein and creates a crevice on the p53 surface that is opposite to the DBD (Joerger et al.”
BackgroundRegulating the p53 pathway: in vitro hypotheses, in vivo veritas
Toledo, F., & Wahl, G. M. (2006) · Nature reviews. Cancer · doi:10.1038/nrc2012 · Cited by 1,286 · see citing works
Post-translational modification of p53 in tumorigenesis
Bode, A. M., & Dong, Z. (2004) · Nature Reviews Cancer · doi:10.1038/nrc1455 · Cited by 1,270 · see citing works
Bond, G. L., Hu, W., Bond, E. E., Robins, H., Lutzker, S. G., Arva, N. C., Bargonetti, J., Bartel, F., Taubert, H., Wuerl, P., et al. (2004) · Cell · doi:10.1016/j.cell.2004.11.022 · Cited by 1,265 · see citing works
Restoration of the tumor suppressor function to mutant p53 by a low-molecular-weight compound
Bykov, V. J. N., Issaeva, N., Shilov, A., Hultcrantz, M., Pugacheva, E., Chumakov, P., Bergman, J., Wiman, K. G., & Selivanova, G. (2002) · Nature Medicine · doi:10.1038/nm0302-282 · Cited by 1,067 · see citing works
The MDM2 gene amplification database
Momand, J. (1998) · Nucleic Acids Research · doi:10.1093/nar/26.15.3453 · Cited by 982 · see citing works
Heise, C. C., Sampson-Johannes, A., Williams, A., McCormick, F. P., Hoff, D. D. V., & Kirn, D. H. (1997) · Nature Medicine · doi:10.1038/nm0697-639 · Cited by 941 · see citing works
p53 isoforms can regulate p53 transcriptional activity
Bourdon, J.-C., Fernandes, K., Murray-Zmijewski, F., Liu, G., Diot, A., Xirodimas, D. P., Saville, M. K., & Lane, D. P. (2005) · Genes & Development · doi:10.1101/gad.1339905 · Cited by 810 · see citing works
Pharmacological Rescue of Mutant p53 Conformation and Function
Foster, B. A., Coffey, H. A., Morin, M. J., & Rastinejad, F. (1999) · Science · doi:10.1126/science.286.5449.2507 · Cited by 802 · see citing works
Small molecule RITA binds to p53, blocks p53–HDM-2 interaction and activates p53 function in tumors
Issaeva, N., Bozko, P. M., Enge, M., Protopopova, M., Verhoef, L. G. G. C., Masucci, M. G., Pramanik, A., & Selivanova, G. (2004) · Nature Medicine · doi:10.1038/nm1146 · Cited by 749 · see citing works
Small-molecule MDM2 antagonists reveal aberrant p53 signaling in cancer: implications for therapy
Tovar, C., Rosinski, J., Filipovic, Z., Higgins, B., Kolinsky, K., Hilton, H., Zhao, X., Vu, B. T., Qing, W., Packman, K., et al. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0507493103 · Cited by 708 · see citing works
Retrovirus–mediated wild–type P53 gene transfer to tumors of patients with lung cancer.
Roth, J. A., Nguyen, D. M., Lawrence, D. D., Kemp, B. L., Carrasco, C. H., Ferson, D. Z., Hong, W. K., Komaki, R. U., Lee, J. J., Nesbitt, J. C., et al. (1996) · Nature Medicine · doi:10.1038/nm0996-985 · Cited by 702 · see citing works
Ding, K., Lu, Y., Nikolovska-Coleska, Z., Wang, G., Qiu, S., Shangary, S., Gao, W., Qin, D., Stuckey, J., Krajewski, K., et al. (2006) · Journal of Medicinal Chemistry · doi:10.1021/jm051122a · Cited by 702 · see citing works
Shangary, S., Qin, D., McEachern, D., Liu, M., Miller, R. S., Qiu, S., Nikolovska-Coleska, Z., Ding, K., Wang, G., Chen, J., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0708917105 · Cited by 660 · see citing works
Structure-based design of potent non-peptide MDM2 inhibitors
Ding, K., Lu, Y., Nikolovska-Coleska, Z., Qiu, S., Ding, Y., Gao, W., Stuckey, J., Krajewski, K., Roller, P. P., Tomita, Y., et al. (2005) · Journal of the American Chemical Society · doi:10.1021/ja051147z · Cited by 657 · see citing works
Vaseva, A. V., & Moll, U. M. (2008) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2008.10.005 · Cited by 618 · see citing works
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 · cited 1× · see citing works
“It could be demonstrated that even established tumours regress after re-expression of endogenous p53 (Martins et al., 2006; Ventura et al., 2007; Xue et al., 2007).”
BackgroundInactivation of the p53 pathway in retinoblastoma
Laurie, N. A., Donovan, S. L., Shih, C.-S., Zhang, J., Mills, N., Fuller, C., Teunisse, A., Lam, S., Ramos, Y., Mohan, A., et al. (2006) · Nature · doi:10.1038/nature05194 · Cited by 595 · see citing works
Regulation of Apoptosis by Alternative Pre-mRNA Splicing
Schwerk, C., & Schulze‐Osthoff, K. (2005) · Molecular Cell · doi:10.1016/j.molcel.2005.05.026 · Cited by 595 · see citing works
Self-citationPRIMA-1 reactivates mutant p53 by covalent binding to the core domain
Lambert, J. M. R., Gorzov, P., Veprintsev, D. B., Söderqvist, M., Segerbäck, D., Bergman, J., Fersht, A. R., Hainaut, P., Wiman, K. G., & Bykov, V. J. N. (2009) · Cancer Cell · doi:10.1016/j.ccr.2009.03.003 · Cited by 592 · see citing works
Tumor Suppressive Functions of p53Preprint
Zilfou, J. T., & Lowe, S. W. (2009) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a001883 · Cited by 572 · see citing works
Reactivation of the p53 Tumor Suppressor Pathway by a Stapled p53 Peptide
Bernal, F., Tyler, A. F., Korsmeyer, S. J., Walensky, L. D., & Verdine, G. L. (2007) · Journal of the American Chemical Society · doi:10.1021/ja0693587 · Cited by 559 · see citing works
p63 mediates survival in squamous cell carcinoma by suppression of p73-dependent apoptosis
Rocco, J. W., Leong, C., Kuperwasser, N., DeYoung, M. P., & Ellisen, L. W. (2006) · Cancer Cell · doi:10.1016/j.ccr.2005.12.013 · Cited by 435 · see citing works
Bullock, A. N., Henckel, J., & Fersht, A. R. (2000) · Oncogene · doi:10.1038/sj.onc.1203434 · Cited by 435 · see citing works
Discovery and Cocrystal Structure of Benzodiazepinedione HDM2 Antagonists That Activate p53 in Cells
Grasberger, B. L., Lu, T., Schubert, C., Parks, D. J., Carver, T. E., Koblish, H. K., Cummings, M. D., LaFrance, L. V., Milkiewicz, K. L., Calvo, R. R., et al. (2005) · Journal of Medicinal Chemistry · doi:10.1021/jm049137g · Cited by 433 · see citing works
MDM2 antagonists induce p53-dependent apoptosis in AML: implications for leukemia therapy
Kojima, K., Konopleva, M. Y., Samudio, I. J., Shikami, M., Cabreira-Hansen, M. D. G., McQueen, T. J., Ruvolo, V. R., Tsao, T., Zeng, Z., Vassilev, L. T., et al. (2005) · Blood · doi:10.1182/blood-2005-02-0553 · Cited by 407 · see citing works
Targeted rescue of a destabilized mutant of p53 by an in silico screened drug
Boeckler, F. M., Joerger, A. C., Jaggi, G., Rutherford, T. J., Veprintsev, D. B., & Fersht, A. R. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0805326105 · Cited by 389 · see citing works
Translating p53 into the clinic
Cheok, C. F., Verma, C. S., Baselga, J., & Lane, D. P. (2011) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2010.174 · Cited by 381 · see citing works
Design of a synthetic Mdm2-binding mini protein that activates the p53 response in vivo
Böttger, A., Böttger, V., Sparks, A., Liu, W.-L., Howard, S. F., & Lane, D. P. (1997) · Current Biology · doi:10.1016/s0960-9822(06)00374-5 · Cited by 363 · see citing works
HdmX stimulates Hdm2-mediated ubiquitination and degradation of p53
Linares, L. K., Hengstermann, A., Ciechanover, A., Müller, S., & Scheffner, M. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2030930100 · Cited by 361 · see citing works
Structural basis for understanding oncogenic p53 mutations and designing rescue drugs
Joerger, A. C., Ang, H. C., & Fersht, A. R. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0607286103 · Cited by 354 · see citing works
p53 isoforms Δ133p53 and p53β are endogenous regulators of replicative cellular senescence
Fujita, K., Mondal, A. M., Horikawa, I., Nguyen, G. H., Kumamoto, K., Sohn, J. J., Bowman, E. D., Mathe, E. A., Schetter, A. J., Pine, S. R., et al. (2009) · Nature Cell Biology · doi:10.1038/ncb1928 · Cited by 336 · see citing works
Danovi, D., Meulmeester, E., Pasini, D., Migliorini, D., Capra, M., Frenk, R., de Graaf, P., Francoz, S., Gasparini, P., Gobbi, A., et al. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.13.5835-5843.2004 · Cited by 310 · see citing works
Soussi, T., Dehouche, K., & Béroud, C. (2000) · Human Mutation · doi:10.1002/(sici)1098-1004(200001)15:1 · Cited by 269 · see citing works
New Approaches and Therapeutics Targeting Apoptosis in Disease
Fischer, U., & Schulze‐Osthoff, K. (2005) · Pharmacological Reviews · doi:10.1124/pr.57.2.6 · Cited by 255 · see citing works
Self-citationTerphenyl‐Based Helical Mimetics That Disrupt the p53/HDM2 Interaction
Yin, H. H., Lee, G., Park, H. S., Payne, G. A., Rodriguez, J. M., Sebti, S. M., & Hamilton, A. D. (2005) · Angewandte Chemie International Edition · doi:10.1002/anie.200462316 · Cited by 254 · see citing works
PRIMA-1MET synergizes with cisplatin to induce tumor cell apoptosis
Bykov, V. J. N., Zache, N., Stridh, H., Westman, J., Bergman, J., Selivanova, G., & Wiman, K. G. (2005) · Oncogene · doi:10.1038/sj.onc.1208419 · Cited by 252 · see citing works
Reactivation of Mutant p53 and Induction of Apoptosis in Human Tumor Cells by Maleimide Analogs
Bykov, V. J. N., Issaeva, N., Zache, N., Shilov, A., Hultcrantz, M., Bergman, J., Selivanova, G., & Wiman, K. G. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m501664200 · Cited by 247 · see citing works
Itahana, K., Mao, H., Jin, A., Itahana, Y., Clegg, H. V., Lindström, M. S., Bhat, K. P., Godfrey, V. L., Evan, G. I., & Zhang, Y. (2007) · Cancer Cell · doi:10.1016/j.ccr.2007.09.007 · Cited by 245 · see citing works
p53-based Cancer TherapyPreprint
Lane, D. P., Cheok, C. F., & Laı́n, S. (2010) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a001222 · Cited by 244 · see citing works
Picksley, S. M., Vojtĕsek, B., Sparks, A., & Lane, D. P. (1994) · PubMed · Cited by 238 · see citing works
Tumor suppression and normal aging in mice with constitutively high p53 activity
Mendrysa, S. M., O'Leary, K. A., McElwee, M. K., Michalowski, J., Eisenman, R. N., Powell, D. A., & Perry, M. E. (2006) · Genes & Development · doi:10.1101/gad.1378506 · Cited by 210 · see citing works
Multimodal action of antitumor agents on DNA: The ellipticine series
Auclair, C. (1987) · Archives of Biochemistry and Biophysics · doi:10.1016/0003-9861(87)90463-2 · Cited by 208 · see citing works
Identification and Characterization of the First Small Molecule Inhibitor of MDMX
Reed, D., Shen, Y., Shelat, A. A., Arnold, L. A., Ferreira, A. M., Zhu, F., Mills, N., Smithson, D. C., Regni, C. A., Bashford, D., et al. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.056747 · Cited by 198 · cited 1× · see citing works
“Interestingly, high-throughput screening of drug libraries recently identified SJ-172550 (CAS 431979-47-4) as a lead compound that interferes with p53:MDMX interaction and showed p53-dependent cytotoxic effects in tumour cell lines (Reed et al., 2010).”
BackgroundHigh metastatic potential in mice inheriting a targeted p53 missense mutation
Liu, G., McDonnell, T. J., Luna, R. M. D. O., Kapoor, M., Mims, B. H., El‐Naggar, A. K., & Lozano, G. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.8.4174 · Cited by 198 · see citing works
Walker, D. R., Bond, J. P., Tarone, R. E., Harris, C. C., Makalowski, W., Boguski, M. S., & Greenblatt, M. S. (1999) · Oncogene · doi:10.1038/sj.onc.1202298 · Cited by 198 · see citing works
Kravchenko, J. E., Ilyinskaya, G. V., Komarov, P. G., Agapova, L. S., Кочетков, Д. В., Strom, E., Frolova, E. I., Kovriga, I. E., Gudkov, A. V., Feinstein, E., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0802091105 · Cited by 191 · see citing works
The dark side of a tumor suppressor: anti-apoptotic p53
Jänicke, R. U., Sohn, D., & Schulze‐Osthoff, K. (2008) · Cell Death and Differentiation · doi:10.1038/cdd.2008.33 · Cited by 188 · see citing works
Self-citationCharacterization of the p53-rescue drug CP-31398 in vitro and in living cells
Rippin, T. M., Bykov, V. J. N., Freund, S. M. V., Selivanova, G., Wiman, K. G., & Fersht, A. R. (2002) · Oncogene · doi:10.1038/sj.onc.1205362 · Cited by 186 · see citing works
Identification of novel mdm2 binding peptides by phage display.
Böttger, V., Böttger, A., Howard, S. F., Picksley, S. M., Chêne, P., Garcı́a-Echeverrı́a, C., Hochkeppel, H. K., & Lane, D. P. (1996) · PubMed · Cited by 182 · see citing works
Parks, D. J., LaFrance, L. V., Calvo, R. R., Milkiewicz, K. L., Gupta, V., Lattanze, J., Ramachandren, K., Carver, T. E., Petrella, E. C., Cummings, M. D., et al. (2004) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2004.11.009 · Cited by 170 · see citing works
Koblish, H. K., Zhao, S., Franks, C. F., Donatelli, R. R., Tominovich, R. M., LaFrance, L. V., Leonard, K. A., Gushue, J. M., Parks, D. J., Calvo, R. R., et al. (2006) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-05-0199 · Cited by 164 · see citing works
Bishop, J. M. (1982) · Advances in cancer research · doi:10.1016/s0065-230x(08)60880-5 · Cited by 163 · see citing works
How Many Mutant p53 Molecules Are Needed To Inactivate a Tetramer?
Chan, W. M., Siu, W. Y., Lau, A. W. S., & Poon, R. Y. C. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.8.3536-3551.2004 · Cited by 159 · see citing works
CP-31398, a novel p53-stabilizing agent, induces p53-dependent and p53-independent glioma cell death
Wischhusen, J., Naumann, U., Ohgaki, H., Rastinejad, F., & Weller, M. (2003) · Oncogene · doi:10.1038/sj.onc.1207198 · Cited by 158 · see citing works
Kinyamu, H. K., & Archer, T. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.16.5867-5881.2003 · Cited by 157 · see citing works
Hardcastle, I. R., Liu, J., Valeur, E., Watson, A. F., Ahmed, S. U., Blackburn, T. J., Bennaceur, K., Clegg, W., Drummond, C. J., Endicott, J., et al. (2011) · Journal of Medicinal Chemistry · doi:10.1021/jm1011929 · Cited by 152 · see citing works
Hardcastle, I. R., Ahmed, S. U., Atkins, H., Farnie, G., Golding, B. T., Griffin, R. J., Guyenne, S., Hutton, C., Källblad, P., Kemp, S. J., et al. (2006) · Journal of Medicinal Chemistry · doi:10.1021/jm0601194 · Cited by 149 · see citing works
The anticancer agent ellipticine on activation by cytochrome P450 forms covalent DNA adducts☆
Stiborová, M., Bieler, C. A., Wießler, M., et al. (2001) · Biochemical Pharmacology · doi:10.1016/s0006-2952(01)00806-1 · Cited by 148 · see citing works
Wang, W., Takimoto, R., Rastinejad, F., & El‐Deiry, W. S. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.6.2171-2181.2003 · Cited by 144 · see citing works
Rescue of mutant p53 transcription function by ellipticine
Peng, Y., Li, C., Chen, L., Sebti, S. M., & Chen, J. (2003) · Oncogene · doi:10.1038/sj.onc.1206777 · Cited by 141 · see citing works
Topoisomerase II Binds to Ellipticine in the Absence or Presence of DNA.
Froelich-Ammon, S. J., Patchan, M. W., Osheroff, N., & Thompson, R. B. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.25.14998 · Cited by 137 · see citing works
Tang, X., Zhu, Y., Han, L., Kim, A. L., Kopelovich, L., Bickers, D. R., & Athar, M. (2007) · Journal of Clinical Investigation · doi:10.1172/jci32481 · Cited by 135 · see citing works
Wang, Y., Suh, Y., Fuller, M. Y., Jackson, J. G., Xiong, S., Terzian, T., Quintás‐Cardama, A., Bankson, J. A., El‐Naggar, A. K., & Lozano, G. (2011) · Journal of Clinical Investigation · doi:10.1172/jci44504 · Cited by 132 · see citing works
Molecular Basis for the Inhibition of p53 by Mdmx
Popowicz, G. M., Czarna, A., Rothweiler, U., Szwagierczak, A., Krajewski, M., Weber, L., & Holak, T. A. (2007) · Cell Cycle · doi:10.4161/cc.6.19.4740 · Cited by 131 · see citing works
The Mutant p53-Conformation Modifying Drug, CP-31398, Can Induce Apoptosis
Takimoto, R., Wang, W., Dicker, D. T., Rastinejad, F., Lyssikatos, J. P., & El‐Deiry, W. S. (2002) · Cancer Biology & Therapy · doi:10.4161/cbt.1.1.41 · Cited by 128 · see citing works
A High-Frequency Regulatory Polymorphism in the p53 Pathway Accelerates Tumor Development
Post, S. M., Quintás-Cardama, A., Pant, V., Iwakuma, T., Hamir, A., Jackson, J. G., Maccio, D. R., Bond, G. L., Johnson, D. G., Levine, A. J., et al. (2010) · Cancer Cell · doi:10.1016/j.ccr.2010.07.010 · Cited by 127 · see citing works
Targeting the ubiquitin‐proteasome system for cancer therapy
Yang, Y., Kitagaki, J., Wang, H., Hou, D., & Perantoni, A. O. (2008) · Cancer Science · doi:10.1111/j.1349-7006.2008.01013.x · Cited by 124 · see citing works
Maerken, T. V., Ferdinande, L., Taildeman, J., Lambertz, I., Yigit, N., Vercruysse, L., Rihani, A., Michaelis, M., Cinatl, J. J., Cuvelier, C. A., et al. (2009) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djp355 · Cited by 120 · see citing works
From ONYX-015 to Armed Vaccinia Viruses: The Education and Evolution of Oncolytic Virus Development
Crompton, A. M., & Kirn, D. H. (2007) · Current Cancer Drug Targets · doi:10.2174/156800907780058862 · Cited by 118 · see citing works
Knappskog, S., Bjørnslett, M., Myklebust, L. M., Huijts, P. E. A., Vreeswijk, M. P. G., Edvardsen, H., Guo, Y., Zhang, X., Yang, M., Ylisaukko‐oja, S. K., et al. (2011) · Cancer Cell · doi:10.1016/j.ccr.2010.12.019 · Cited by 118 · see citing works
A Small-Molecule Inhibitor of MDMX Activates p53 and Induces Apoptosis
Wang, H., Ma, X., Ren, S., Buolamwini, J. K., & Yan, C. (2011) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-10-0581 · Cited by 117 · see citing works
Mutant p53 targeting by the low molecular weight compound STIMA‐1
Zache, N., Lambert, J. M. R., Rökaeus, N., Shen, J., Hainaut, P. L., Bergman, J., Wiman, K. G., & Bykov, V. J. N. (2008) · Molecular Oncology · doi:10.1016/j.molonc.2008.02.004 · Cited by 116 · see citing works
Lu, Y., Nikolovska‐Coleska, Z., Fang, X., Gao, W., Shangary, S. K., Qiu, S., Qin, D., & Wang, S. (2006) · Journal of Medicinal Chemistry · doi:10.1021/jm060023+ · Cited by 115 · see citing works
Demma, M. J., Maxwell, E., Ramos, R., Liang, L., Li, C., Hesk, D., Rossman, R. R., Mallams, A. K., Doll, R. J., Liu, M., et al. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.083469 · Cited by 107 · see citing works
p53 α-Helix mimetics antagonize p53/MDM2 interaction and activate p53
Chen, L., Yin, H. H., Farooqi, B., Sebti, S. M., Hamilton, A. D., & Chen, J. (2005) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-04-0342 · Cited by 97 · see citing works
NMR indicates that the small molecule RITA does not block p53-MDM2 binding in vitro
Krajewski, M., Ozdowy, P., D’Silva, L., Rothweiler, U., & Holak, T. A. (2005) · Nature Medicine · doi:10.1038/nm1105-1135 · Cited by 96 · see citing works
The functional domains in p53 family proteins exhibit both common and distinct properties
Harms, K. L., & Chen, X. (2006) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4401904 · Cited by 96 · see citing works
Ritter, T., Lehmann, M., & Volk, H. (2002) · BioDrugs · doi:10.2165/00063030-200216010-00001 · Cited by 95 · see citing works
Galatin, P. S., & Abraham, D. J. (2004) · Journal of Medicinal Chemistry · doi:10.1021/jm034182u · Cited by 90 · see citing works
Yang, Z., Wang, D., Wang, G., et al. (2009) · Journal of Cancer Research and Clinical Oncology · doi:10.1007/s00432-009-0701-6 · Cited by 86 · see citing works
Tumor suppression by p53: making cells senescent.
Qian, Y., & Chen, X. (2010) · PubMed · doi:10.14670/hh-25.515 · Cited by 85 · see citing works
Shi, L. M., Myers, T. G., Fan, Y., O'Connor, P. M., Paull, K. D., Friend, S. H., & Weinstein, J. N. (1998) · Molecular Pharmacology · doi:10.1124/mol.53.2.241 · Cited by 78 · see citing works
Kojima, K., Burks, J. K., Arts, J., & Andreeff, M. (2010) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-10-0337 · Cited by 78 · see citing works
Mohammad, R. M., Wu, J., Azmi, A. S., Aboukameel, A., Sosin, A. M., Wu, S., Yang, D., Wang, S., & Al-Katib, A. M. (2009) · Molecular Cancer · doi:10.1186/1476-4598-8-115 · Cited by 77 · see citing works
What have animal models taught us about the p53 pathway?
Lozano, G., & Zambetti, G. P. (2005) · The Journal of Pathology · doi:10.1002/path.1704 · Cited by 76 · see citing works
Parks, D. J., LaFrance, L. V., Calvo, R. R., Milkiewicz, K. L., Marugán, J., Raboisson, P., Schubert, C., Koblish, H. K., Zhao, S., Franks, C. F., et al. (2006) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2006.03.055 · Cited by 76 · see citing works
Canner, J. A., Sobo, M., Ball, S. L., Hutzen, B. J., Deangelis, S., Willis, W. L., Studebaker, A. W., Ding, K., Wang, S., Yang, D., et al. (2009) · British Journal of Cancer · doi:10.1038/sj.bjc.6605199 · Cited by 72 · see citing works
Stabilization of mutant p53 via alkylation of cysteines and effects on DNA binding
Kaar, J. L., Basse, N., Joerger, A. C., Stephens, E., Rutherford, T. J., & Fersht, A. R. (2010) · Protein Science · doi:10.1002/pro.507 · Cited by 71 · see citing works
Regulation of the p53 pathway by ubiquitin and related proteins
Hock, A., & Vousden, K. H. (2010) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2010.06.011 · Cited by 69 · see citing works
Demma, M. J., Wong, S., Maxwell, E., & Dasmahapatra, B. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m401854200 · Cited by 65 · see citing works
Sugikawa, E., Hosoi, T., Yazaki, N., et al. (2000) · PubMed · Cited by 61 · see citing works
Graupner, V., Alexander, E., Overkamp, T., Rothfuss, O. C., Laurenzi, V. D., Gillissen, B. F., Daniel, P. T., Schulze‐Osthoff, K., & Eßmann, F. (2011) · Cell Death and Differentiation · doi:10.1038/cdd.2010.179 · Cited by 60 · see citing works
Self-citationIrradiation-induced Translocation of p53 to Mitochondria in the Absence of Apoptosis
Eßmann, F., Pohlmann, S., Gillissen, B. F., Daniel, P. T., Schulze‐Osthoff, K., & Jänicke, R. U. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m502052200 · Cited by 57 · see citing works
Self-citationLoss-of-function genetics in mammalian cells: the p53 tumor suppressor model
Carnero, A. (2000) · Nucleic Acids Research · doi:10.1093/nar/28.11.2234 · Cited by 53 · see citing works
Functional characterization of p53β and p53γ, two isoforms of the tumor suppressor p53
Graupner, V., Schulze‐Osthoff, K., Eßmann, F., & Jänicke, R. U. (2009) · Cell Cycle · doi:10.4161/cc.8.8.8251 · Cited by 44 · see citing works
Self-citationSuppression of Familial Adenomatous Polyposis by CP-31398, a TP53 Modulator, in APCmin/+ Mice
Rao, C. V., Swamy, M. V., Patlolla, J. M. R., & Kopelovich, L. (2008) · Cancer Research · doi:10.1158/0008-5472.can-08-1610 · Cited by 42 · see citing works
An update on gene therapy in China.
Shi, J., & Zheng, D. (2009) · PubMed · Cited by 42 · see citing works
Sun, S. H., Zheng, M., Ding, K., Wang, S., & Sun, Y. (2008) · Cancer Biology & Therapy · doi:10.4161/cbt.7.6.5841 · Cited by 36 · see citing works
Comparison of Molecular Strategies for Breast Cancer Virotherapy Using Oncolytic Adenovirus
Bazán‐Peregrino, M., Carlisle, R. C., Hernández-Alcoceba, R., Iggo, R. D., Homicskó, K., Fisher, K. D., Halldén, G., Mautner, V., Shen, Y., & Seymour, L. W. (2008) · Human Gene Therapy · doi:10.1089/hum.2008.047 · Cited by 35 · see citing works
The do's and don'ts of p53 isoforms
Jänicke, R. U., Graupner, V., Budach, W., & Eßmann, F. (2009) · Biological Chemistry · doi:10.1515/bc.2009.093 · Cited by 31 · see citing works
Rao, C. V., Steele, V. E., Swamy, M. V., Patlolla, J. M. R., Guruswamy, S., & Kopelovich, L. (2009) · Cancer Research · doi:10.1158/0008-5472.can-09-1377 · Cited by 30 · see citing works
An Information-Theoretic Analysis of Genetics, Gender and Age in Cancer Patients
Atwal, G. S., Rabadán, R., Lozano, G., Strong, L. C., Ruijs, M., Schmidt, M. K., Veer, L. J. V., Nevanlinna, H. A., Tommiska, J., Aittomäki, K., et al. (2008) · PLoS ONE · doi:10.1371/journal.pone.0001951 · Cited by 24 · see citing works
Flagged first, then by citations
Research works printed but not linked: 3
- BJP Targeting the p53 pathway for anti-cancer therapy British Journal of Pharmacology (2012) 165 328-344 341 14765381, 2012, 2, Downloaded from https://bpspubs.onlinelibrary.wiley.com/doi/10.1111/j.1476-5381.2011.01570.x, Wiley Online Library on [04/01/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
- BJP F Essmann and K Schulze-Osthoff 342 British Journal of Pharmacology (2012) 165 328-344 14765381, 2012, 2, Downloaded from https://bpspubs.onlinelibrary.wiley.com/doi/10.1111/j.1476-5381.2011.01570.x, Wiley Online Library on [04/01/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
- BJP Targeting the p53 pathway for anti-cancer therapy British Journal of Pharmacology (2012) 165 328-344 343 14765381, 2012, 2, Downloaded from https://bpspubs.onlinelibrary.wiley.com/doi/10.1111/j.1476-5381.2011.01570.x, Wiley Online Library on [04/01/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
Cited by
Sorted by citations
The role of tumour-stromal interactions in modifying drug response: challenges and opportunities
McMillin, D. W., Negri, J. M., & Mitsiades, C. S. (2013) · Nature Reviews Drug Discovery · doi:10.1038/nrd3870 · Cited by 474 · see citing works
Conradt, L., Henrich, A., Wirth, M., Reichert, M., Lesina, M., Algül, H., Schmid, R. M., Krämer, O. H., Saur, D., & Schneider, G. (2013) · International Journal of Cancer · doi:10.1002/ijc.27916 · Cited by 30 · see citing works
- Authors
- Essmann, F., & Schulze‐Osthoff, K.
- Affiliations
- University of Tübingen (DE)
- Corresponding author
- Schulze‐Osthoff, Klaus
- Venue
- British Journal of Pharmacology
- Publisher
- Wiley
- Published
- 2011-12-16
- Volume
- 165
- Issue
- 2
- Pages
- 328-344
- ISSN
- 0007-1188 (ISSN-L)
- 1476-5381
- PMC
- PMC3268188
- OpenAlex
- W1595856931
- Cited by
- 77
- References
- 114
- Citations by year
- 2025: 1 · 2024: 3 · 2023: 3 · 2022: 6 · 2021: 5 · 2020: 1 · 2019: 3 · 2018: 6 · 2017: 4 · 2016: 7 · 2015: 9 · 2014: 10 · 2013: 12 · 2012: 7
- FWCI
- 0.85
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- British Journal of Pharmacology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Deutsche Forschungsgemeinschaft
- Deutsche Krebshilfe
- Topics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
- Keywords
- p53 pathway, p53 reactivation, MDM2, oncolytic viruses, adenoviral gene therapy, apoptosis, cellular senescence, cancer therapy
- MeSH terms
- Animals, Antineoplastic Agents, Humans, Indoles, Mutation, Neoplasms, Pyrrolidinones, Protein Biosynthesis, Tumor Suppressor Protein p53, Proto-Oncogene Proteins c-mdm2
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