Cited by 914Cancer-related Molecular PathwaysPI3K/AKT/mTOR signaling in cancerCancer Mechanisms and Therapy

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Awakening guardian angels: drugging the p53 pathway

Brown, Christopher J., Lain, Sonia, Verma, Chandra S., Fersht, Alan R., Lane, David P.·2009·Nature Reviews Cancer

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Abstract

Currently, around 11 million people are living with a tumour that contains an inactivating mutation of TP53 (the human gene that encodes p53) and another 11 million have tumours in which the p53 pathway is partially abrogated through the inactivation of other signalling or effector components. The p53 pathway is therefore a prime target for new cancer drug development, and several original approaches to drug discovery that could have wide applications to drug development are being used. In one approach, molecules that activate p53 by blocking protein-protein interactions with MDM2 are in early clinical development. Remarkable progress has also been made in the development of p53-binding molecules that can rescue the function of certain p53 mutants. Finally, cell-based assays are being used to discover compounds that exploit the p53 pathway by either seeking targets and compounds that show synthetic lethality with TP53 mutations or by looking for non-genotoxic activators of the p53 response.

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Activating Mutations in the Epidermal Growth Factor Receptor Underlying Responsiveness of Non–Small-Cell Lung Cancer to Gefitinib
Lynch, T. J., Bell, D. W., Sordella, R., Gurubhagavatula, S., Okimoto, R. A., Brannigan, B. W., Harris, P. L., Haserlat, S. M., Supko, J. G., Haluska, F. G., et al. (2004) · New England Journal of Medicine · doi:10.1056/nejmoa040938 · Cited by 11,486
EGFR Mutations in Lung Cancer: Correlation with Clinical Response to Gefitinib Therapy
Paez, J. G., Jänne, P. A., Lee, J. C., Tracy, S., Greulich, H., Gabriel, S., Herman, P., Kaye, F. J., Lindeman, N., Boggon, T. J., et al. (2004) · Science · doi:10.1126/science.1099314 · Cited by 9,368
Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy
Farmer, H., McCabe, N., Lord, C. J., Tutt, A. N. J., Johnson, D. A., Richardson, T. B., Santarosa, M., Dillon, K. J., Hickson, I., Knights, C., et al. (2005) · Nature · doi:10.1038/nature03445 · Cited by 6,683
p53, guardian of the genome
Lane, D. P. (1992) · Nature · doi:10.1038/358015a0 · Cited by 5,138
Self-citation
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
EGF receptor gene mutations are common in lung cancers from “never smokers” and are associated with sensitivity of tumors to gefitinib and erlotinib
Pao, W., Miller, V., Zakowski, M., Doherty, J., Politi, K., Sarkaria, I., Singh, B., Heelan, R., Rusch, V., Fulton, L., et al. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0405220101 · Cited by 4,338
An inhibitor of Bcl-2 family proteins induces regression of solid tumours
Oltersdorf, T., Elmore, S. W., Shoemaker, A. R., Armstrong, R. C., Augeri, D. J., Belli, B., Bruncko, M., Deckwerth, T. L., Dinges, J., Hajduk, P. J., et al. (2005) · Nature · doi:10.1038/nature03579 · Cited by 3,407
The mdm-2 oncogene product forms a complex with the p53 protein and inhibits p53-mediated transactivation
Momand, J., Zambetti, G. P., Olson, D. C., George, D., & Levine, A. J. (1992) · Cell · doi:10.1016/0092-8674(92)90644-r · Cited by 3,113
hSIR2SIRT1 Functions as an NAD-Dependent p53 Deacetylase
Vaziri, H., Dessain, S. K., Eaton, E. N., Imai, S., Frye, R. A., Pandita, T. K., Guarente, L., & Weinberg, R. A. (2001) · Cell · doi:10.1016/s0092-8674(01)00527-x · Cited by 2,690
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
p53 in health and disease
Vousden, K. H., & Lane, D. P. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2147 · Cited by 2,351
Self-citation
Negative Control of p53 by Sir2α Promotes Cell Survival under Stress
Luo, J., Nikolaev, A. Y., Imai, S.-I., Chen, D., Su, F., Shiloh, A., Guarente, L., & Gu, W. (2001) · Cell · doi:10.1016/s0092-8674(01)00524-4 · Cited by 2,081
A Hot Spot of Binding Energy in a Hormone-Receptor Interface
Clackson, T., & Wells, J. A. (1995) · Science · doi:10.1126/science.7529940 · Cited by 1,987
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
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
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 · cited 1×
“A series of genetic models has, however, established that the restoration of p53 activity in established tumour cells is an exceptionally effective interventio”
Background
The PARP superfamily
Amé, J., Spenlehauer, C., & de MURCIA, G. (2004) · BioEssays · doi:10.1002/bies.20085 · Cited by 1,463
Rescue of early embryonic lethality in mdm2-deficient mice by deletion of p53
de Oca Luna, R. M., Wagner, D. S., & Lozano, G. (1995) · Nature · doi:10.1038/378203a0 · Cited by 1,420 · cited 1×
“Genetic studies indicate that MDM2 and MDM4 have non-redundant functions to keep p53 inactive during embryogenesis and throughout developmen”
Background
Glivec (STI571, imatinib), a rationally developed, targeted anticancer drug
Capdeville, R., Buchdunger, E., Zimmermann, J., & Matter, A. (2002) · Nature Reviews Drug Discovery · doi:10.1038/nrd839 · Cited by 1,409
p53 Target Genes Sestrin1 and Sestrin2 Connect Genotoxic Stress and mTOR Signaling
Budanov, A. V., & Karin, M. (2008) · Cell · doi:10.1016/j.cell.2008.06.028 · Cited by 1,326 · cited 1×
“Other new targets of p53-induced transcription have been identified that are involved in protein translatio”
Background
Rescue of embryonic lethality in Mdm2-deficient mice by absence of p53
Jones, S. N., Roe, A. E., Donehower, L. A., & Bradley, A. (1995) · Nature · doi:10.1038/378206a0 · Cited by 1,280 · cited 1×
“Therefore, Trp53 −/− Mdm2 −/− mice are viable, whereas Trp53 +/− Mdm2 −/− results in embryonic lethality; this is also the case for Mdm4 −/− mic”
Novel anticancer targets: revisiting ERBB2 and discovering ERBB3
Baselga, J. M., & Swain, S. M. (2009) · Nature reviews. Cancer · doi:10.1038/nrc2656 · Cited by 1,170
Modulation of microRNA processing by p53
Suzuki, H. I., Yamagata, K., Sugimoto, K., Iwamoto, T., Kato, S., & Miyazono, K. (2009) · Nature · doi:10.1038/nature08199 · Cited by 1,158
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
Mdm2 Is a RING Finger-dependent Ubiquitin Protein Ligase for Itself and p53
Fang, S., Jensen, J. P., Ludwig, R. L., Vousden, K. H., & Weissman, A. M. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.12.8945 · Cited by 1,044
Leptomycin B inactivates CRM1/exportin 1 by covalent modification at a cysteine residue in the central conserved region
Kudo, N. R., Matsumori, N., Taoka, H., Fujiwara, D., Schreiner, E. P., Wolff, B., Yoshida, M., & Horinouchi, S. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.16.9112 · Cited by 1,033
Resistance to therapy caused by intragenic deletion in BRCA2
Edwards, S. L., Brough, R., Lord, C. J., Natrajan, R., Vatcheva, R., Levine, D. A., Boyd, J., Reis-Filho, J. S., & Ashworth, A. (2008) · Nature · doi:10.1038/nature06548 · Cited by 1,011
p53 and Human Cancer: The First Ten Thousand Mutations
Hainaut, P. L., & Hollstein, M. C. (1999) · Advances in cancer research · doi:10.1016/s0065-230x(08)60785-x · Cited by 999
The MDM2 gene amplification database
Momand, J. (1998) · Nucleic Acids Research · doi:10.1093/nar/26.15.3453 · Cited by 982
Regulation of the specific DNA binding function of p53
Hupp, T. R., Meek, D. W., Midgley, C., & Lane, D. P. (1992) · Cell · doi:10.1016/0092-8674(92)90562-q · Cited by 916
Self-citation
Human SIR2 deacetylates p53 and antagonizes PML/p53‐induced cellular senescence
Langley, E., Pearson, M., Faretta, M., Bauer, U., Frye, R. A., Minucci, S., Pelicci, P. G., & Kouzarides, T. (2002) · The EMBO Journal · doi:10.1093/emboj/21.10.2383 · Cited by 859
Modelling Myc inhibition as a cancer therapy
Soucek, L., Whitfield, J. R., Martins, C. P., Finch, A. J., Murphy, D. J., Sodir, N. M., Karnezis, A. N., Swigart, L. B., Nasi, S., & Evan, G. I. (2008) · Nature · doi:10.1038/nature07260 · Cited by 846
Disruption of the nucleolus mediates stabilization of p53 in response to DNA damage and other stresses
Rubbi, C. P., & Milner, J. (2003) · The EMBO Journal · doi:10.1093/emboj/cdg579 · Cited by 828
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
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 760
Structural Biology of the Tumor Suppressor p53
Joerger, A. C., & Fersht, A. R. (2008) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.77.060806.091238 · Cited by 726
Self-citation
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
Structure-Based Design of Spiro-oxindoles as Potent, Specific Small-Molecule Inhibitors of the MDM2−p53 Interaction
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
Oncogenic mutations of the p53 tumor suppressor: the demons of the guardian of the genome.
Sigal, A., & Rotter, V. (2000) · PubMed · Cited by 669
Temporal activation of p53 by a specific MDM2 inhibitor is selectively toxic to tumors and leads to complete tumor growth inhibition
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
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
The ARF/p53 pathway.
Sherr, C. J., & Weber, J. D. (2000) · Current Opinion in Genetics & Development · doi:10.1016/s0959-437x(99)00038-6 · Cited by 654
The Regulation of AMPK β1, TSC2, and PTEN Expression by p53: Stress, Cell and Tissue Specificity, and the Role of These Gene Products in Modulating the IGF-1-AKT-mTOR Pathways
Feng, Z., Hu, W., de Stanchina, E., Teresky, A. K., Jin, S., Lowe, S., & Levine, A. J. (2007) · Cancer Research · doi:10.1158/0008-5472.can-06-4149 · Cited by 633
Regulation of HDM2 activity by the ribosomal protein L11
Lohrum, M. A. E., Ludwig, R. L., Kubbutat, M. H. G., Hanlon, M., & Vousden, K. H. (2003) · Cancer Cell · doi:10.1016/s1535-6108(03)00134-x · Cited by 626
Small-Molecule Inhibitors of the MDM2-p53 Protein-Protein Interaction to Reactivate p53 Function: A Novel Approach for Cancer Therapy
Shangary, S., & Wang, S. (2009) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.48.113006.094723 · Cited by 623
Cotranslation of activated mutant p53 with wild type drives the wild-type p53 protein into the mutant conformation
Milner, J., & Medcalf, E. (1991) · Cell · doi:10.1016/0092-8674(91)90384-b · Cited by 612
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×
“A series of genetic models has, however, established that the restoration of p53 activity in established tumour cells is an exceptionally effective interventio”
Background
Inactivation 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
PRIMA-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
Self-citation
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 563
p53: traffic cop at the crossroads of DNA repair and recombination
Sengupta, S., & Harris, C. C. (2005) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1546 · Cited by 544
MDM2 inhibitors for cancer therapy
Vassilev, L. T. (2007) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2006.11.002 · Cited by 532
A reversible, p53-dependent G0/G1 cell cycle arrest induced by ribonucleotide depletion in the absence of detectable DNA damage.Preprint
Linke, S. P., Clarkin, K., Leonardo, A. D., Tsou, A.-P., & Wahl, G. M. (1996) · Genes & Development · doi:10.1101/gad.10.8.934 · Cited by 531
Discovery, In Vivo Activity, and Mechanism of Action of a Small-Molecule p53 Activator
Laı́n, S., Hollick, J. J., Campbell, J., Staples, O. D., Higgins, M., Aoubala, M., McCarthy, A. R., Appleyard, V. C. L., Murray, K. E., Baker, L., et al. (2008) · Cancer Cell · doi:10.1016/j.ccr.2008.03.004 · Cited by 530
Self-citation
Rescue of embryonic lethality in Mdm4-null mice by loss of Trp53 suggests a nonoverlapping pathway with MDM2 to regulate p53
Parant, J., Chavez-Reyes, A., Little, N. A., Yan, W., Reinke, V., Jochemsen, A. G., & Lozano, G. (2001) · Nature Genetics · doi:10.1038/ng714 · Cited by 517
Base Excision Repair Is Impaired in Mammalian Cells Lacking Poly(ADP-ribose) Polymerase-1
Dantzer, F., de la Rubia, G., Murcia, J. M., Hostomský, Z., de MURCIA, G., & Schreiber, V. (2000) · Biochemistry · doi:10.1021/bi0003442 · Cited by 505
Transcription-independent pro-apoptotic functions of p53
Moll, U. M., Wolff, S., Speidel, D., & Deppert, W. (2005) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2005.09.007 · Cited by 468
Quantitative analysis of residual folding and DNA binding in mutant p53 core domain: definition of mutant states for rescue in cancer therapy
Bullock, A. N., Henckel, J., & Fersht, A. R. (2000) · Oncogene · doi:10.1038/sj.onc.1203434 · Cited by 440
Self-citation
Small peptides activate the latent sequence-specific DNA binding function of p53
Hupp, T. R., Sparks, A., & Lane, D. P. (1995) · Cell · doi:10.1016/0092-8674(95)90165-5 · Cited by 439
Self-citation
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
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 398
Self-citation
Structural basis for high-affinity peptide inhibition of p53 interactions with MDM2 and MDMX
Pazgier, M., Liu, M., Zou, G., Yuan, W., Li, C., Li, C., Li, J., Monbo, J., Zella, D., Tarasov, S. G., et al. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0900947106 · Cited by 391
Activity of MDM2, a ubiquitin ligase, toward p53 or itself is dependent on the RING finger domain of the ligase
Honda, R., & Yasuda, H. (2000) · Oncogene · doi:10.1038/sj.onc.1203464 · Cited by 376
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 368
Self-citation
The inherent instability of mutant p53 is alleviated by Mdm2 or p16 INK4a lossPreprint
Terzian, T., Suh, Y., Iwakuma, T., Post, S. M., Neumann, M., Lang, G. A., Pelt, C. S. V., & Lozano, G. (2008) · Genes & Development · doi:10.1101/gad.1662908 · Cited by 363
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
The Human ARF Cell Cycle Regulatory Gene Promoter Is a CpG Island Which Can Be Silenced by DNA Methylation and Down-Regulated by Wild-Type p53
Robertson, K. D., & Jones, P. A. (1998) · Molecular and Cellular Biology · doi:10.1128/mcb.18.11.6457 · Cited by 352
Restoration of the growth suppression function of mutant p53 by a synthetic peptide derived from the p53 C-terminal domain
Selivanova, G., Iotsova, V., Okan, İ., Fritsche, M., Ström, M., Groner, B., Grafström, R. C., & Wiman, K. G. (1997) · Nature Medicine · doi:10.1038/nm0697-632 · Cited by 341
Small molecule inhibitors of HDM2 ubiquitin ligase activity stabilize and activate p53 in cells
Yang, Y., Ludwig, R. L., Jensen, J. P., Pierre, S. A., Medaglia, M. V., Davydov, I. V., Safiran, Y. J., Oberoi, P., Kenten, J. H., Phillips, A. C., et al. (2005) · Cancer Cell · doi:10.1016/j.ccr.2005.04.029 · Cited by 327
MDM2 interacts with MDMX through their RING finger domains
Tanimura, S., Ohtsuka, S., Mitsui, K., Shirouzu, K., Yoshimura, A., & Ohtsubo, M. (1999) · FEBS Letters · doi:10.1016/s0014-5793(99)00254-9 · Cited by 324
Discovering novel ligands for macromolecules using X-ray crystallographic screening
Nienaber, V. L., Richardson, P. L., Klighofer, V., Bouska, J. J., Giranda, V. L., & Greer, J. (2000) · Nature Biotechnology · doi:10.1038/80319 · Cited by 322
Amplification of Mdmx (or Mdm4 ) Directly Contributes to Tumor Formation by Inhibiting p53 Tumor Suppressor Activity
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
Comparison between single-dose and divided-dose administration of dactinomycin and doxorubicin for patients with Wilms' tumor: a report from the National Wilms' Tumor Study Group.
Green, D. M., Breslow, N. E., Beckwith, J. B., Finklestein, J. Z., Grundy, P. E., Thomas, P. R. M., Kim, T., Shochat, S. J., Haase, G. M., Ritchey, M. L., et al. (1998) · Journal of Clinical Oncology · doi:10.1200/jco.1998.16.1.237 · Cited by 305
A panel of isogenic human cancer cells suggests a therapeutic approach for cancers with inactivated p53
Sur, S., Pagliarini, R. A., Bunz, F., Rago, C., Diaz, L. A., Kinzler, K. W., Vogelstein, B., & Papadopoulos, N. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0813333106 · Cited by 293
Structure of the MDM2/MDMX RING domain heterodimer reveals dimerization is required for their ubiquitylation in trans
Linke, K., Mace, P. D., Smith, C. A., Vaux, D. L., Silke, J., & Day, C. L. (2008) · Cell Death & Differentiation · doi:10.1038/sj.cdd.4402309 · Cited by 288
Inhibition of RNA polymerase II as a trigger for the p53 response
Ljungman, M. E., Zhang, F., Chen, F., Rainbow, A. J., & McKay, B. C. (1999) · Oncogene · doi:10.1038/sj.onc.1202356 · Cited by 287
Stabilization of the MDM2 Oncoprotein by Interaction with the Structurally Related MDMX Protein
Sharp, D. A., Kratowicz, S. A., Sank, M. J., & George, D. L. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.53.38189 · Cited by 286
Targeting lysosomal degradation induces p53-dependent cell death and prevents cancer in mouse models of lymphomagenesis
Maclean, K. H., Dorsey, F. C., Cleveland, J. L., & Kastan, M. B. (2007) · Journal of Clinical Investigation · doi:10.1172/jci33700 · Cited by 281
Mutant p53: an oncogenic transcription factor
Strano, S., Dell’Orso, S., Agostino, S. D., Fontemaggi, G., Sacchi, A., & Blandino, G. (2007) · Oncogene · doi:10.1038/sj.onc.1210296 · Cited by 272
Small molecules that reactivate p53 in renal cell carcinoma reveal a NF-κB-dependent mechanism of p53 suppression in tumors
Gurova, K. V., Hill, J. E., Guo, C., Prokvolit, A., Burdelya, L. G., Samoylova, E. M., Khodyakova, A. V., Ganapathi, R. N., Ganapathi, M. K., Tararova, N. D., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0508888102 · Cited by 266
Mutual Dependence of MDM2 and MDMX in Their Functional Inactivation of p53
Gu, J., Kawai, H., Nie, L., Kitao, H., Wiederschain, D., Jochemsen, A. G., Parant, J. M., Lozano, G., & Yuan, Z.-M. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.c200150200 · Cited by 265
Phase I trial of elactocin
Newlands, E. S., Rustin, G. J. S., & Brampton, M. (1996) · British Journal of Cancer · doi:10.1038/bjc.1996.415 · Cited by 253
p53 Protein Exhibits 3′-to-5′ Exonuclease Activity
Mummenbrauer, T., Janus, F., Müller, B., Wiesmüller, L., Deppert, W., & Große, F. (1996) · Cell · doi:10.1016/s0092-8674(00)81309-4 · Cited by 253
Dissecting cellular processes using small molecules: identification of colchicine-like, taxol-like and other small molecules that perturb mitosis
Haggarty, S. J., Mayer, T. U., Miyamoto, D. T., Fathi, R., King, R. W., Mitchison, T. J., & Schreiber, S. L. (2000) · Chemistry & Biology · doi:10.1016/s1074-5521(00)00101-0 · Cited by 251
Amplification and overexpression of the MDM4 (MDMX) gene from 1q32 in a subset of malignant gliomas without TP53 mutation or MDM2 amplification.
Riemenschneider, M. J., Büschges, R., Wolter, M., REIFENBERGER, J., Boström, J. P., Kraus, J. A., Schlegel, U. S., & Reifenberger, G. (1999) · PubMed · Cited by 247
MDM2 promotes ubiquitination and degradation of MDMX
Pan, Y., & Chen, J. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.15.5113-5121.2003 · Cited by 246 · cited 1×
“Another consequence of MDM2–MDM4 heterodimerization is that MDM4 can be ubiquitylated by MDM2and is consequently degrade”
Background
Tumor Suppressor p53: Analysis of Wild-Type and Mutant p53 Complexes
Milner, J., Medcalf, E., & Cook, A. (1991) · Molecular and Cellular Biology · doi:10.1128/mcb.11.1.12 · Cited by 243
Mdmx stabilizes p53 and Mdm2 via two distinct mechanisms
Stad, R., Little, N. A., Xirodimas, D. P., Frenk, R., van der Eb, A. J., Lane, D. P., Saville, M. K., & Jochemsen, A. G. (2001) · The EMBO Reports · doi:10.1093/embo-reports/kve227 · Cited by 234
Self-citation
Mutant conformation of p53
Stephen, C. W., & Lane, D. P. (1992) · Journal of Molecular Biology · doi:10.1016/0022-2836(92)90386-x · Cited by 211
Self-citation
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
What the papers say: The p53‐mdm2 autoregulatory feedback loop: A paradigm for the regulation of growth control by p53?
Picksley, S. M., & Lane, D. P. (1993) · BioEssays · doi:10.1002/bies.950151008 · Cited by 207
Self-citation
Treatment of Terminal Peritoneal Carcinomatosis by a Transducible p53-Activating Peptide
Snyder, E. L., Meade, B. R., Saenz, C. C., & Dowdy, S. F. (2004) · PLoS Biology · doi:10.1371/journal.pbio.0020036 · Cited by 206
Suppression of the Deubiquitinating Enzyme USP5 Causes the Accumulation of Unanchored Polyubiquitin and the Activation of p53
Dayal, S., Sparks, A., Jacob, J., Allende-Vega, N., Lane, D. P., & Saville, M. K. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m805871200 · Cited by 203
Self-citation
Activation of p53 by MDM2 Antagonists Can Protect Proliferating Cells from Mitotic Inhibitors
Carvajal, D. M., Tovar, C., Yang, H. S., Vu, B. T., Heimbrook, D. C., & Vassilev, L. T. (2005) · Cancer Research · doi:10.1158/0008-5472.can-04-3576 · Cited by 202
Identification of Nuclear Export Inhibitors with Potent Anticancer Activity In vivo
Mutka, S. C., Yang, W. Q., Dong, S. D., Ward, S. L., Craig, D. A., Timmermans, P. B. M. W. M., & Murli, S. (2009) · Cancer Research · doi:10.1158/0008-5472.can-08-0858 · Cited by 195
An shRNA barcode screen provides insight into cancer cell vulnerability to MDM2 inhibitors
Brummelkamp, T. R., Fabius, A. W. M., Mullenders, J., Madiredjo, M., Velds, A., Kerkhoven, R. M., Bernards, R., & Beijersbergen, R. L. (2006) · Nature Chemical Biology · doi:10.1038/nchembio774 · Cited by 190
Comparative study of the p53-mdm2 and p53-MDMX interfaces
Böttger, V., Böttger, A., Garcia-Echeverria, C., Ramos, Y. F., van der Eb, A. J., Jochemsen, A. G., & Lane, D. P. (1999) · Oncogene · doi:10.1038/sj.onc.1202281 · Cited by 189
Self-citation
Characterization 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
Self-citation
The ability of human papillomavirus E6 proteins to target p53 for degradation in vivo correlates with their ability to abrogate actinomycin D-induced growth arrest
Foster, S. A., Demers, G. W., Etscheid, B. G., & Galloway, D. A. (1994) · Journal of Virology · doi:10.1128/jvi.68.9.5698-5705.1994 · Cited by 185
No PUMA, no death
Yu, J., & Zhang, L. (2003) · Cancer Cell · doi:10.1016/s1535-6108(03)00249-6 · Cited by 182
A Single Nucleotide Polymorphism in the MDM2 Gene: From a Molecular and Cellular Explanation to Clinical Effect
Bond, G. L., Hu, W., & Levine, A. J. (2005) · Cancer Research · doi:10.1158/0008-5472.can-05-0825 · Cited by 176
Control of p53 ubiquitination and nuclear export by MDM2 and ARF.
Zhang, Y., & Xiong, Y. (2001) · PubMed · Cited by 176
Are interactions with p63 and p73 involved in mutant p53 gain of oncogenic function?
Li, Y., & Prives, C. L. (2007) · Oncogene · doi:10.1038/sj.onc.1210311 · Cited by 174
MDM2-Dependent Downregulation of p21 and hnRNP K Provides a Switch between Apoptosis and Growth Arrest Induced by Pharmacologically Activated p53
Enge, M., Bao, W., Hedström, E., Jackson, S. P., Moumen, A., & Selivanova, G. (2009) · Cancer Cell · doi:10.1016/j.ccr.2009.01.019 · Cited by 172
Targeting Mdm2 and Mdmx in cancer therapy: better living through medicinal chemistry?
Wade, M., & Wahl, G. M. (2009) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-08-0423 · Cited by 170
Benzodiazepinedione inhibitors of the Hdm2:p53 complex suppress human tumor cell proliferation in vitro and sensitize tumors to doxorubicin in vivo
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 167
DNA damage-induced MDMX degradation is mediated by MDM2
Kawai, H., Wiederschain, D., Kitao, H., Stuart, J., Tsai, K. K. C., & Yuan, Z.-M. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m308295200 · Cited by 163 · cited 1×
“Another consequence of MDM2–MDM4 heterodimerization is that MDM4 can be ubiquitylated by MDM2and is consequently degrade”
Background
Cancer-Associated Mutations in the MDM2 Zinc Finger Domain Disrupt Ribosomal Protein Interaction and Attenuate MDM2-Induced p53 Degradation
Lindström, M. S., Jin, A., Deisenroth, C., Wolf, G. W., & Zhang, Y. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.01307-06 · Cited by 149
Aberrant expression of HDMX proteins in tumor cells correlates with wild-type p53.
Ramos, Y. F., Stad, R. K., Attema, J., Peltenburg, L. T. C., van der Eb, A. J., & Jochemsen, A. G. (2001) · PubMed · Cited by 147
p53 accumulates but is functionally impaired when DNA synthesis is blocked
Gottifredi, V., Shieh, S.-Y., Taya, Y., & Prives, C. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.98.3.1036 · Cited by 147
Hdmx protein stability is regulated by the ubiquitin ligase activity of Mdm2
de Graaf, P., Little, N. A., Ramos, Y. F. M., Meulmeester, E., Letteboer, S. J. F., & Jochemsen, A. G. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m213034200 · Cited by 143 · cited 1×
“Another consequence of MDM2–MDM4 heterodimerization is that MDM4 can be ubiquitylated by MDM2and is consequently degrade”
Background
Specific activation of the p53 pathway by low dose actinomycin D: A new route to p53 based cyclotherapy
Choong, M. L., Yang, H. C., Lee, M. A., & Lane, D. P. (2009) · Cell Cycle · doi:10.4161/cc.8.17.9503 · Cited by 141
Self-citation
Reactivation of Mutant p53 through Interaction of a C-Terminal Peptide with the Core Domain
Selivanova, G., Ryabchenko, L. G., Jansson, E. Å., Iotsova, V., & Wiman, K. G. (1999) · Molecular and Cellular Biology · doi:10.1128/mcb.19.5.3395 · Cited by 139
p14ARF silencing by promoter hypermethylation mediates abnormal intracellular localization of MDM2.
Esteller, M., Cordon‐Cardo, C., Corn, P. G., Meltzer, S. J., Pohar, K. S., Watkins, D. N., Capellá, G., Peinado, M. A., Matías‐Guiu, X., Prat, J., et al. (2001) · PubMed · Cited by 132
Mycophenolic Acid Activation of p53 Requires Ribosomal Proteins L5 and L11
Sun, X., Dai, M., & Lu, H. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m801387200 · Cited by 120
Ablation of Key Oncogenic Pathways by RITA-Reactivated p53 Is Required for Efficient Apoptosis
Grinkevich, V. V., Nikulenkov, F., Shi, Y., Enge, M., Bao, W., Malyukova, A., Gluch, A., Kel, A. E., Sangfelt, O., & Selivanova, G. (2009) · Cancer Cell · doi:10.1016/j.ccr.2009.03.021 · Cited by 118
Recombinant adenovirus expressing wild-type p53 is antiangiogenic: a proposed mechanism for bystander effect.
Nishizaki, M., Fujiwara, T., Tanida, T., HIZUTA, A., Nishimori, H., Tokino, T., Nakamura, Y., Bouvet, M., Roth, J., & Tanaka, N. (1999) · PubMed · Cited by 118
Conformational and Molecular Basis for Induction of Apoptosis by a p53 C-terminal Peptide in Human Cancer Cells
Kim, A. L., Raffo, A. J., Brandt‐Rauf, P. W., Pincus, M. R., Monaco, R. R., Abarzúa, P., & Fine, R. L. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.49.34924 · Cited by 114
The Spectrum of Mutations at the p53 Locus
Levine, A. J., Wu, M. C., Chang, A., Silver, A., Attiyeh, E. F., Lin, J., & Epstein, C. B. (1995) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1995.tb12115.x · Cited by 106
Cancer Specific Viruses and the Development of ONYX-015
McCormick, F. P. (2003) · Cancer Biology & Therapy · doi:10.4161/cbt.216 · Cited by 106
Transcriptional activities of mutant p53: When mutations are more than a loss
Kim, E. L., & Deppert, W. (2004) · Journal of Cellular Biochemistry · doi:10.1002/jcb.20271 · Cited by 102
p53 functions in the incorporation step in DNA base excision repair in mouse liver mitochondria
de Souza-Pinto, N. C., Harris, C. C., & Bohr, V. A. (2004) · Oncogene · doi:10.1038/sj.onc.1207874 · Cited by 101
High affinity interaction of the p53 peptide-analogue with human Mdm2 and Mdmx
Czarna, A., Popowicz, G. M., Pęcak, A., Wolf, S., Dubin, G., & Holak, T. A. (2009) · Cell Cycle · doi:10.4161/cc.8.8.8185 · Cited by 99
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
Significance of HDMX‐S (or MDM4) mRNA splice variant overexpression and HDMX gene amplification on primary soft tissue sarcoma prognosis
Bartel, F., Schulz, J., Böhnke, A., Blümke, K., Kappler, M., Bache, M., Schmidt, H., Würl, P., Taubert, H. W., & Hauptmann, S. (2005) · International Journal of Cancer · doi:10.1002/ijc.21206 · Cited by 93
Flexibility: the key to p53 function?
Milner, J. (1995) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(00)88954-9 · Cited by 88
Small-Molecule Activation of p53 Blocks Hypoxia-Inducible Factor 1α and Vascular Endothelial Growth Factor Expression In Vivo and Leads to Tumor Cell Apoptosis in Normoxia and Hypoxia
Yang, J., Ahmed, A., Poon, E., Perusinghe, N. P., Brandon, A. D. H., Box, G., Valenti, M. R., Eccles, S. A., Rouschop, K. M. A., Wouters, B. G., et al. (2009) · Molecular and Cellular Biology · doi:10.1128/mcb.00959-08 · Cited by 85
Increased Radioresistance and Accelerated B Cell Lymphomas in Mice with Mdmx Mutations that Prevent Modifications by DNA-Damage-Activated Kinases
Wang, Y. V., Leblanc, M., Wade, M., Jochemsen, A. G., & Wahl, G. M. (2009) · Cancer Cell · doi:10.1016/j.ccr.2009.05.008 · Cited by 79
A new anti-p53 monoclonal antibody, previously reported to be directed against the large T antigen of simian virus 40.
Milner, J., Cook, A., & Sheldon, M. J. (1987) · PubMed · Cited by 78
Enhanced pharmacokinetic properties of 1,4-benzodiazepine-2,5-dione antagonists of the HDM2-p53 protein–protein interaction through structure-based drug design
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 77
DNA Protein Cross-Links Produced by NSC 652287, a Novel Thiophene Derivative Active Against Human Renal Cancer Cells
Nieves‐Neira, W., Rivera, M. I., Kohlhagen, G., Hursey, M. L., Pourquier, P., Sausville, E. A., & Pommier, Y. G. (1999) · Molecular Pharmacology · doi:10.1124/mol.56.3.478 · Cited by 70
Cyclin-Dependent Kinase Inhibitors Sensitize Tumor Cells to Nutlin-Induced Apoptosis: a Potent Drug Combination
Cheok, C. F., Dey, A., & Lane, D. P. (2007) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-07-0161 · Cited by 69
Self-citation
Structure-based design of molecular cancer therapeutics
van Montfort, R. L. M., & Workman, P. (2009) · Trends in biotechnology · doi:10.1016/j.tibtech.2009.02.003 · Cited by 68
Family Feud in Chemosensitvity: p73 and Mutant p53
Irwin, M. S. (2004) · Cell Cycle · doi:10.4161/cc.3.3.768 · Cited by 63
Novel 1,4-benzodiazepine-2,5-diones as Hdm2 antagonists with improved cellular activity
Leonard, K. A., Marugán, J., Raboisson, P., Calvo, R. R., Gushue, J. M., Koblish, H. K., Lattanze, J., Zhao, S., Cummings, M. D., Player, M. R., et al. (2006) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2006.04.009 · Cited by 61
RNA synthesis block by 5,6-dichloro-1-β-D-ribofuranosylbenzimidazole (DRB) triggers p53-dependent apoptosis in human colon carcinoma cells
Poele, R. T., Okorokov, A. L., & Joel, S. P. (1999) · Oncogene · doi:10.1038/sj.onc.1202961 · Cited by 60
Selective toxicity of the tricyclic thiophene NSC 652287 in renal carcinoma cell lines
Rivera, M. I., Stinson, S. F., Vistica, D. T., Jorden, J. L., Kenney, S., & Sausville, E. A. (1999) · Biochemical Pharmacology · doi:10.1016/s0006-2952(99)00046-5 · Cited by 55
p53 Modulates RPA-Dependent and RPA-Independent WRN Helicase Activity
Sommers, J. A., Sharma, S., Doherty, K. M., Karmakar, P., Yang, Q., Kenny, M. K., Harris, C. C., & Brosh, R. M. (2005) · Cancer Research · doi:10.1158/0008-5472.can-03-0231 · Cited by 54
Pilot screening programme for small molecule activators of p53
Berkson, R., Hollick, J. J., Westwood, N. J., Woods, J. A., Lane, D. P., & Laı́n, S. (2005) · International Journal of Cancer · doi:10.1002/ijc.20968 · Cited by 52
Self-citation
High-throughput measurement of the Tp53 response to anticancer drugs and random compounds using a stably integrated Tp53-responsive luciferase reporter
Sohn, T. A., Bansal, R. K., Su, G. H., Murphy, K. M., & Kern, S. E. (2002) · Carcinogenesis · doi:10.1093/carcin/23.6.949 · Cited by 49
Tumor Suppressing Gene Therapy
Fang, B., & Roth, J. A. (2003) · Cancer Biology & Therapy · doi:10.4161/cbt.210 · Cited by 47
Dissection of the sequence-specific DNA binding and exonuclease activities reveals a superactive yet apoptotically impaired mutant p53 protein
Ahn, J., Poyurovsky, M. V., Baptiste, N., Beckerman, R., Cain, C. R., Mattia, M., McKinney, K. M., Zhou, J., Zupnick, A., Gottifredi, V., et al. (2009) · Cell Cycle · doi:10.4161/cc.8.10.8548 · Cited by 30
Curing Cancer with p53
Lane, D. P. (2004) · New England Journal of Medicine · doi:10.1056/nejmcibr041288 · Cited by 21
Self-citation
Characterization, chemical optimization and anti-tumor activity of a tubulin poison identified by a p53-based phenotypic screen
Staples, O. D., Hollick, J. J., Campbell, J., Higgins, M., McCarthy, A. R., Appleyard, V. C. L., Murray, K. E., Baker, L., Thompson, A. M., Ronseaux, S., et al. (2008) · Cell Cycle · doi:10.4161/cc.7.21.6982 · Cited by 15
Self-citation
Activation of a unique p53-dependent DNA damage response
Yang, J., Ahmed, A., & Ashcroft, M. A. (2009) · Cell Cycle · doi:10.4161/cc.8.10.8326 · Cited by 15
Activation of p53 by scaffold-stabilised expression of Mdm2-binding peptides: visualisation of reporter gene induction at the single-cell level
Karlsson, G. B., Jensen, A., Stevenson, L. F., Woods, Y. L., Lane, D. P., & Sørensen, M. S. (2004) · British Journal of Cancer · doi:10.1038/sj.bjc.6602143 · Cited by 14
Self-citation
Basic Cell Cycle and Cancer Research: Is Harmony Possible?
Blagosklonny, M. V. (2002) · Cell Cycle · doi:10.4161/cc.1.1.92 · Cited by 5
Nobel Prize: Heroes for a Heroic Age
Johnson, R. T., & Downes, C. S. (2002) · Cell Cycle · doi:10.4161/cc.1.1.93 · Cited by 2

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Rufini, A., Tucci, P., Celardo, I., & Melino, G. (2013) · Oncogene · doi:10.1038/onc.2012.640 · Cited by 798

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Authors: Brown, C. J., Lain, S., Verma, C. S., Fersht, A. R., & Lane, D. P.
Affiliations: Agency for Science, Technology and Research (SG)
Medical Research Council (GB)
Corresponding author: Lane, David P.
ORCID: Brown, Christopher J.
Verma, Chandra S.
Lane, David P.
Venue: Nature Reviews Cancer
Publisher: Springer Science and Business Media LLC
Published: 2009-12
Volume: 9
Issue: 12
Pages: 862-873
ISSN: 1474-175X (ISSN-L)
1474-1768
DOI: 10.1038/nrc2763
OpenAlex: W2093775600
Cited by: 881
References: 149
Citations by year: 2026: 5 · 2025: 24 · 2024: 21 · 2023: 64 · 2022: 27 · 2021: 32 · 2020: 37 · 2019: 49 · 2018: 42 · 2017: 59 · 2016: 58 · 2015: 76 · 2014: 91 · 2013: 74 · 2012: 82
FWCI: 6.45
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Nature reviews. Cancer (publishedVersion)
PubMed (publishedVersion)
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 › Cancer Research › Cancer Mechanisms and Therapy
Keywords: p53 pathway, TP53 mutation, MDM2, p53 activation, mutant p53, synthetic lethality, cell-based assays, anticancer drug development, protein-protein interaction inhibitors
MeSH terms: Antineoplastic Agents, Humans, Mutation, Neoplasms, Drug Design, Signal Transduction, Genes, p53, Tumor Suppressor Protein p53, Drug Delivery Systems, Proto-Oncogene Proteins c-mdm2

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Awakening guardian angels: drugging the p53 pathway

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