Adaptation of cancer cells from different entities to the MDM2 inhibitor nutlin-3 results in the emergence of p53-mutated multi-drug-resistant cancer cells
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Six p53 wild-type cancer cell lines from infrequently p53-mutated entities (neuroblastoma, rhabdomyosarcoma, and melanoma) were continuously exposed to increasing concentrations of the murine double minute 2 inhibitor nutlin-3, resulting in the emergence of nutlin-3-resistant, p53-mutated sublines displaying a multi-drug resistance phenotype. Only 2 out of 28 sublines adapted to various cytotoxic drugs harboured p53 mutations. Nutlin-3-adapted UKF-NB-3 cells (UKF-NB-3(r)Nutlin(10 μM), harbouring a G245C mutation) were also radiation resistant. Analysis of UKF-NB-3 and UKF-NB-3(r)Nutlin(10 μM) cells by RNA interference experiments and lentiviral transduction of wild-type p53 into p53-mutated UKF-NB-3(r)Nutlin(10 μM) cells revealed that the loss of p53 function contributes to the multi-drug resistance of UKF-NB-3(r)Nutlin(10 μM) cells. Bioinformatics PANTHER pathway analysis based on microarray measurements of mRNA abundance indicated a substantial overlap in the signalling pathways differentially regulated between UKF-NB-3(r)Nutlin(10 μM) and UKF-NB-3 and between UKF-NB-3 and its cisplatin-, doxorubicin-, or vincristine-resistant sublines. Repeated nutlin-3 adaptation of neuroblastoma cells resulted in sublines harbouring various p53 mutations with high frequency. A p53 wild-type single cell-derived UKF-NB-3 clone was adapted to nutlin-3 in independent experiments. Eight out of ten resulting sublines were p53-mutated harbouring six different p53 mutations. This indicates that nutlin-3 induces de novo p53 mutations not initially present in the original cell population. Therefore, nutlin-3-treated cancer patients should be carefully monitored for the emergence of p53-mutated, multi-drug-resistant cells.
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Cancers can develop resistance to drugs that destroy them and can acquire compensatory TP53 mutations.
“cancers have a unique ability to develop resistance to drugs that cause their destruction and subsequently acquired compensatory TP53 mutations (Aziz, et al., 2011; Michaelis, et al., 2011)”
From The Mdm network and its regulation of p53 activities: a rheostat of cancer risk (2014) · cites this paper as Michaelis, et al., 2011
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Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing
Benjamini, Y., & Hochberg, Y. (1995) · Journal of the Royal Statistical Society Series B: Statistical Methodology · doi:10.1111/j.2517-6161.1995.tb02031.x · Cited by 109,482 · see citing works
Smyth, G. K. (2004) · Statistical Applications in Genetics and Molecular Biology · doi:10.2202/1544-6115.1027 · Cited by 11,829 · see citing works
When mutants gain new powers: News from the mutant p53 field
Brosh, R., & Rotter, V. (2009) · Nature Reviews Cancer · doi:10.1038/nrc2693 · Cited by 1,132 · see citing works
Dissecting Therapeutic Resistance to RAF Inhibition in Melanoma by Tumor Genomic Profiling
Wagle, N., Emery, C., Berger, M. F., Davis, M. J., Sawyer, A. M., Pochanard, P., Kehoe, S. M., Johannessen, C. M., MacConaill, L. E., Hahn, W. C., et al. (2011) · Journal of Clinical Oncology · doi:10.1200/jco.2010.33.2312 · Cited by 996 · see citing works
MDM2 inhibitors for cancer therapy
Vassilev, L. T. (2007) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2006.11.002 · Cited by 532 · see citing works
Drug-Selected Human Lung Cancer Stem Cells: Cytokine Network, Tumorigenic and Metastatic Properties
Levina, V. V., Marrangoni, A., DeMarco, R., Gorelik, E., & Lokshin, A. E. (2008) · PLoS ONE · doi:10.1371/journal.pone.0003077 · Cited by 407 · see citing works
Mi, H., Guo, N., Kejariwal, A., & Thomas, P. D. (2006) · Nucleic Acids Research · doi:10.1093/nar/gkl869 · Cited by 372 · see citing works
A Multicolor Panel of Novel Lentiviral “Gene Ontology” (LeGO) Vectors for Functional Gene Analysis
Riecken, K., Bartsch, U., Stocking, C., & Fehse, B. (2008) · Molecular Therapy · doi:10.1038/mt.2008.6 · Cited by 352 · see citing works
Self-citationResistance to Targeted Therapies: Refining Anticancer Therapy in the Era of Molecular Oncology
Ellis, L. M., & Hicklin, D. J. (2009) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-09-1070 · Cited by 248 · see citing works
Loss of p53 function confers high-level multidrug resistance in neuroblastoma cell lines.
Keshelava, N., Zuo, J. J., Chen, P., Waidyaratne, S. N., Luna, M. C., Gomer, C. J., Triche, T. J., & Reynolds, C. P. (2001) · PubMed · Cited by 232 · see citing works
Smalley, K. S. M., Contractor, R., Haass, N. K., Kulp, A. N., Atilla‐Gokcumen, G. E., Williams, D. S., Bregman, H. S., Flaherty, K. T., Soengas, M. S., Meggers, E., et al. (2007) · Cancer Research · doi:10.1158/0008-5472.can-06-1538 · Cited by 229 · see citing works
Sklar, C. A., Mertens, A. C., Walter, A. W., Mitchell, D. S., Nesbit, M. E., O’Leary, M., Hutchinson, R. J., Meadows, A. T., & Robison, L. L. (2000) · Medical and Pediatric Oncology · doi:10.1002/1096-911x(200008)35:2 · Cited by 214 · see citing works
The p53 pathway and its inactivation in neuroblastoma
Tweddle, D. A., Pearson, A. D. J., Haber, M., Norris, M. D., Xue, C., Flemming, C. L., & Lunec, J. (2003) · Cancer Letters · doi:10.1016/s0304-3835(03)00088-0 · Cited by 171 · see citing works
Ambrosini, G., Sambol, E. B., Carvajal, D., Vassilev, L. T., Singer, S., & Schwartz, G. K. (2007) · Oncogene · doi:10.1038/sj.onc.1210136 · Cited by 163 · see citing works
High Frequency of p53/MDM2/p14ARF Pathway Abnormalities in Relapsed Neuroblastoma
Carr‐Wilkinson, J., O’Toole, K., Wood, K. M., Challen, C., Baker, A., Julian Board, Evans, L. E., Cole, M. F., Cheung, N. V., Boos, J., et al. (2010) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-09-1865 · Cited by 162 · see citing works
Reactivation of p53: from peptides to small molecules
Brown, C. J., Cheok, C. F., Verma, C. S., & Lane, D. P. (2010) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2010.11.004 · Cited by 135 · see citing works
Acquisition of p53 mutations in response to the non-genotoxic p53 activator Nutlin-3
Aziz, M. H., Shen, H., & Maki, C. G. (2011) · Oncogene · doi:10.1038/onc.2011.185 · Cited by 131 · see citing works
Association of EGFR Gene Amplification and CDKN2 (p16/MTS1) Gene Deletion in Glioblastoma Multiforme
Hayashi, Y., Ueki, K., Waha, A., Wiestler, O. D., Louis, D. N., & von Deimling, A. (1997) · Brain Pathology · doi:10.1111/j.1750-3639.1997.tb00890.x · Cited by 128 · see citing works
Transcription, genomes, function
Cho, R. J., & Campbell, M. J. (2000) · Trends in Genetics · doi:10.1016/s0168-9525(00)02065-5 · Cited by 126 · 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
Self-citationCarr, J., Bell, E., Pearson, A. D. J., Kees, U. R., Beris, H., Lunec, J., & Tweddle, D. A. (2006) · Cancer Research · doi:10.1158/0008-5472.can-05-2623 · Cited by 119 · see citing works
Anti-cancer effects of artesunate in a panel of chemoresistant neuroblastoma cell lines
Michaelis, M., Kleinschmidt, M. C., Barth, S., Rothweiler, F., Geiler, J., Rainer Breitling, A., Mayer, B., Deubzer, H. E., Witt, O., Kreuter, J., et al. (2009) · Biochemical Pharmacology · doi:10.1016/j.bcp.2009.08.013 · Cited by 110 · see citing works
Self-citationMichaelis, M., Rothweiler, F., Klassert, D., von Deimling, A., Riecken, K., Fehse, B., Kammerer, B., Doerr, H. W., & Cinatl, J. J. (2009) · Cancer Research · doi:10.1158/0008-5472.can-08-1856 · Cited by 101 · see citing works
Self-citationMiyachi, M., Kakazu, N., Yagyu, S., Katsumi, Y., Tsubai-Shimizu, S., Kikuchi, K., Tsuchiya, K., Iehara, T., & Hosoi, H. (2009) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-08-2955 · Cited by 101 · see citing works
Ray, R. M., Bhattacharya, S., & Johnson, L. R. (2010) · APOPTOSIS · doi:10.1007/s10495-010-0538-0 · Cited by 100 · see citing works
The role of p53 in pigmentation, tanning and melanoma
Box, N. F., & Terzian, T. (2008) · Pigment Cell & Melanoma Research · doi:10.1111/j.1755-148x.2008.00495.x · Cited by 95 · see citing works
The oncogenic roles of p53 mutants in mouse models
Lozano, G. (2007) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2006.12.003 · Cited by 85 · see citing works
Rieger, K. M., Little, A. F., Swart, J., Kastrinakis, W. V., Fitzgerald, J., Hess, D. T., Libertino, J., & Summerhayes, I. C. (1995) · British Journal of Cancer · doi:10.1038/bjc.1995.394 · Cited by 83 · see citing works
A p53-independent role for the MDM2 antagonist Nutlin-3 in DNA damage response initiation
Valentine, J. M., Kumar, S., & Moumen, A. (2011) · BMC Cancer · doi:10.1186/1471-2407-11-79 · Cited by 77 · see citing works
DNA damage response to the Mdm2 inhibitor Nutlin-3
Verma, R., Rigatti, M. J., Belinsky, G. S., Godman, C. A., & Giardina, C. A. (2009) · Biochemical Pharmacology · doi:10.1016/j.bcp.2009.09.020 · Cited by 76 · see citing works
Kotchetkov, R., Činátl, J., Blaheta, R. A., Vogel, J., Karásková, J., Squire, J. A., Driever, P. H., Klingebiel, T. E., & Cinatl, J. J. (2003) · International Journal of Cancer · doi:10.1002/ijc.10917 · Cited by 72 · see citing works
Self-citationCanner, 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
Maerken, T. V., Rihani, A., Dreidax, D., Clercq, S. D., Yigit, N., Marine, J., Westermann, F., Paepe, A. D., Vandesompele, J., & Speleman, F. (2011) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-10-1090 · Cited by 72 · see citing works
Kotchetkov, R., Driever, P. H., Činátl, J., Michaelis, M., Karásková, J., Blaheta, R. A., Squire, J. A., von Deimling, A., Moog, J., & Cinatl, J. J. (2005) · International Journal of Oncology · doi:10.3892/ijo.27.4.1029 · Cited by 68 · see citing works
Self-citationShen, H., Moran, D. M., & Maki, C. G. (2008) · Cancer Research · doi:10.1158/0008-5472.can-08-1901 · Cited by 61 · see citing works
Rothweiler, F., Michaelis, M., Brauer, P., Otte, J., Riecken, K., Fehse, B., Doerr, H. W., Wiese, M., Kreuter, J., Al‐Abed, Y., et al. (2010) · Neoplasia · doi:10.1593/neo.10856 · Cited by 58 · see citing works
Self-citationSpectrum of p53 Tumor Suppressor Gene Mutations and Breast Cancer Survival
Lai, H. C., Ma, F., Trapido, E. J., Meng, L., & Lai, S. (2004) · Breast Cancer Research and Treatment · doi:10.1023/b:brea.0000010699.53742.60 · Cited by 34 · see citing works
West Nile Virus Infection Induces Interferon Signalling in Human Retinal Pigment Epithelial Cells
Cínatl, J. (2006) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.05-1022 · Cited by 24 · see citing works
Multiple mutations of the p53 gene in human mammary carcinoma
Meng, L., Lin, L., Zhang, H., Nassiri, M., Morales, A. R., & Nadji, M. (1999) · Mutation Research/DNA Repair · doi:10.1016/s0921-8777(99)00053-1 · Cited by 22 · see citing works
Selective Enrichment of Hepatocellular Cancer Stem Cells by Chemotherapy
Tan, S. W., Chen, J., Sun, L., & Yao, H.-R. (2009) · Journal of International Medical Research · doi:10.1177/147323000903700409 · Cited by 18 · see citing works
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Drugging p53 in cancer: one protein, many targets
Hassin, O., & Oren, M. (2022) · Nature Reviews Drug Discovery · doi:10.1038/s41573-022-00571-8 · Cited by 736 · see citing works
Drugging the p53 pathway: understanding the route to clinical efficacy
Khoo, K. H., Verma, C. S., & Lane, D. P. (2014) · Nature Reviews Drug Discovery · doi:10.1038/nrd4236 · Cited by 723 · see citing works
The MDM2-p53 pathway revisited
Nag, S. A., Jiangjiang, Q., Kalkunte, S. S., Ming-hai, W., & Zhang, R. (2013) · Journal of Biomedical Research · doi:10.7555/jbr.27.20130030 · Cited by 414 · see citing works
p53 Family and Cellular Stress Responses in Cancer
Pflaum, J., Schlosser, S., & ller, M. M. ⁄. (2014) · Frontiers in Oncology · doi:10.3389/fonc.2014.00285 · Cited by 294 · see citing works
p53 as a target for the treatment of cancer
Duffy, M. J., Synnott, N. C., McGowan, P. M., Crown, J. P., O’Connor, D. P., & Gallagher, W. M. (2014) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2014.10.004 · Cited by 230 · see citing works
Zhu, H., Gao, H., Ji, Y., Zhou, Q., Du, Z., Tian, L., Jiang, Y., Yao, K., & Zhou, Z. (2022) · Journal of Hematology & Oncology · doi:10.1186/s13045-022-01314-3 · Cited by 223 · see citing works
Therapeutic targeting of tumor suppressor genes
Morris, L. G. T., & Chan, T. A.-T. (2014) · Cancer · doi:10.1002/cncr.29140 · Cited by 201 · see citing works
SAMHD1 is a biomarker for cytarabine response and a therapeutic target in acute myeloid leukemia
Schneider, C., Oellerich, T., Baldauf, H., Schwarz, S.-M., Thomas, D., Flick, R., Bohnenberger, H., Kaderali, L., Stegmann, L., Cremer, A., et al. (2016) · Nature Medicine · doi:10.1038/nm.4255 · Cited by 177 · see citing works
Self-citationSarin, N., Engel, F., Kalayda, G. V., Mannewitz, M., Cinatl, J. J., Rothweiler, F., Michaelis, M., Saafan, H., Ritter, C. A., Jaehde, U., et al. (2017) · PLoS ONE · doi:10.1371/journal.pone.0181081 · Cited by 169 · see citing works
Self-citationThe role of DNA damage responses in p53 biology
Speidel, D. (2015) · Archives of Toxicology · doi:10.1007/s00204-015-1459-z · Cited by 165 · see citing works
Self-citationInhibition of p53 inhibitors: progress, challenges and perspectives
Sanz, G., Singh, M., Peuget, S., & Selivanova, G. (2019) · Journal of Molecular Cell Biology · doi:10.1093/jmcb/mjz075 · Cited by 137 · see citing works
Overcoming anti-cancer drug resistance via restoration of tumor suppressor gene function
Gao, L., Wu, Z., Assaraf, Y. G., Chen, Z., & Wang, L. (2021) · Drug Resistance Updates · doi:10.1016/j.drup.2021.100770 · Cited by 118 · see citing works
Zhao, F., Vakhrusheva, O., Markowitsch, S. D., Slade, K. S., Tsaur, I., Cinatl, J. J., Michaelis, M., Efferth, T., Haferkamp, A., & Juengel, E. (2020) · Cells · doi:10.3390/cells9122643 · Cited by 117 · see citing works
Self-citationPicco, G., Cattaneo, C. M., van Vliet, E. J., Crisafulli, G., Rospo, G., Consonni, S., Vieira, S. F., Sánchez-Rodríguez, I., Cancelliere, C., Banerjee, R., et al. (2021) · Cancer Discovery · doi:10.1158/2159-8290.cd-20-1508 · Cited by 112 · see citing works
Self-citationNRF2 and p53: Januses in cancer?
Rotblat, B., Melino, G., & Knight, R. A. (2012) · Oncotarget · doi:10.18632/oncotarget.754 · Cited by 109 · see citing works
Targeting the p53-MDM2 pathway for neuroblastoma therapy: Rays of hope
Zafar, A., Wang, W., Liu, G., Xian, W., McKeon, F., Zhou, J., & Zhang, R. (2020) · Cancer Letters · doi:10.1016/j.canlet.2020.09.023 · Cited by 107 · see citing works
Das, C. K., Linder, B., Bonn, F., Rothweiler, F., Đikić, I., Michaelis, M., Cinatl, J. J., Mandal, M., & Kögel, D. (2018) · Neoplasia · doi:10.1016/j.neo.2018.01.001 · Cited by 105 · see citing works
Self-citationKhurana, A., & Shafer, D. A. (2019) · OncoTargets and Therapy · doi:10.2147/ott.s172315 · Cited by 105 · see citing works
TP53 mutations emerge with HDM2 inhibitor SAR405838 treatment in de-differentiated liposarcoma
Jung, J., Lee, J. S., Dickson, M. A., Schwartz, G. K., Cesne, A. L., Varga, A., Bahleda, R., Wagner, A. J., Choy, E., Jonge, M. J. D., et al. (2016) · Nature Communications · doi:10.1038/ncomms12609 · Cited by 99 · see citing works
Aptamer grafted nanoparticle as targeted therapeutic tool for the treatment of breast cancer
Sheikh, A., Md, S., & Kesharwani, P. (2021) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2021.112530 · Cited by 90 · see citing works
CRISPR-Cas9–based target validation for p53-reactivating model compounds
Wanzel, M., Vischedyk, J. B., Gittler, M. P., Gremke, N., Seiz, J. R., Hefter, M., Noack, M., Savai, R., Mernberger, M., Charles, J. P., et al. (2015) · Nature Chemical Biology · doi:10.1038/nchembio.1965 · Cited by 87 · see citing works
Self-citationYoshimura, M., Ishizawa, J., Ruvolo, V. R., Dilip, A., Quintás‐Cardama, A., McDonnell, T. J., Neelapu, S. S., Kwak, L. W., Shacham, S., Kauffman, M. G., et al. (2014) · Cancer Science · doi:10.1111/cas.12430 · Cited by 88 · see citing works
Arnhold, V., Schmelz, K., Proba, J., Winkler, A., Wünschel, J., Toedling, J., Deubzer, H. E., Künkele, A., Eggert, A., Schulte, J. H., et al. (2018) · Oncotarget · doi:10.18632/oncotarget.23409 · Cited by 85 · see citing works
Identification of flubendazole as potential anti-neuroblastoma compound in a large cell line screen
Michaelis, M., Agha, B., Rothweiler, F., Löschmann, N., Voges, Y., Mittelbronn, M. G. A., Starzetz, T., Harter, P. N., Abhari, B. A., Fulda, S., et al. (2015) · Scientific Reports · doi:10.1038/srep08202 · Cited by 86 · see citing works
Self-citationTargeting p53-MDM2-MDMX Loop for Cancer Therapy
Zhang, Q., Zeng, S. X., & Lu, H. (2014) · Sub-cellular biochemistry/Subcellular biochemistry · doi:10.1007/978-94-017-9211-0_16 · Cited by 83 · see citing works
Selective protection of normal cells from chemotherapy, while killing drug-resistant cancer cells
Blagosklonny, M. V. (2023) · Oncotarget · doi:10.18632/oncotarget.28382 · Cited by 83 · see citing works
Pharmacological reactivation of p53 as a strategy to treat cancer
Zawacka‐Pankau, J., & Selivanova, G. (2015) · Journal of Internal Medicine · doi:10.1111/joim.12336 · Cited by 82 · see citing works
Chen, L., Rousseau, R. F., Middleton, S. A., NICHOLS, G. L., Newell, D. R., Lunec, J., & Tweddle, D. A. (2015) · Oncotarget · doi:10.18632/oncotarget.3504 · Cited by 80 · see citing works
The Mdm network and its regulation of p53 activities: a rheostat of cancer risk
Eischen, C. M., & Lozano, G. (2014) · Human Mutation · doi:10.1002/humu.22524 · Cited by 79 · see citing works
Onafuye, H., Pieper, S., Mulac, D., Cinatl, J. J., Wass, M. N., Langer, K., & Michaelis, M. (2019) · Beilstein Journal of Nanotechnology · doi:10.3762/bjnano.10.166 · Cited by 78 · see citing works
Self-citationProlonged Idasanutlin (RG7388) Treatment Leads to the Generation of p53-Mutated Cells
Skalniak, Ł., Kocik-Krol, J., Polak, J., Skalniak, A., Rak, M., Wolnicka-Głubisz, A., & Holak, T. A. (2018) · Cancers · doi:10.3390/cancers10110396 · Cited by 76 · see citing works
miR-20a induces cisplatin resistance of a human gastric cancer cell line via targeting CYLD
Zhu, M., Xin Min, Z. H. O. U., Du, Y., Huang, Z., Zhu, J., Xu, J., Cheng, G., Shu, Y., Liu, P., Zhu, W., et al. (2016) · Molecular Medicine Reports · doi:10.3892/mmr.2016.5413 · Cited by 67 · see citing works
Hároníková, L., Bonczek, O., Zatloukalová, P., Kokas, F. Z., Kucerikova, M., Coates, P. J., Fåhræus, R., & Vojtěšek, B. (2021) · Cellular & Molecular Biology Letters · doi:10.1186/s11658-021-00293-6 · Cited by 71 · see citing works
Role of p53 circuitry in tumorigenesis: A brief review
Niazi, S., Purohit, M., & Niazi, J. H. (2018) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2018.08.099 · Cited by 65 · see citing works
Wild type p53 reactivation: From lab bench to clinic
Selivanova, G. (2014) · FEBS Letters · doi:10.1016/j.febslet.2014.03.049 · Cited by 65 · see citing works
Regulation of p73 activity by post-translational modifications
Conforti, F., Sayan, E., Sreekumar, R., & Sayan, B. S. (2012) · Cell Death and Disease · doi:10.1038/cddis.2012.27 · Cited by 64 · see citing works
p63 is an alternative p53 repressor in melanoma that confers chemoresistance and a poor prognosis
Matin, R., Chikh, A., Chong, S. L. P., Mesher, D., Graf, M., Sanzà, P., Senatore, V., Scatolini, M., Moretti, F., Leigh, I. M., et al. (2013) · The Journal of Experimental Medicine · doi:10.1084/jem.20121439 · Cited by 65 · see citing works
Burmakin, M., Shi, Y., Hedström, E., Kogner, P., & Selivanova, G. (2013) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-12-2211 · Cited by 63 · see citing works
Preukschas, M., Hagel, C., Schulte, A., Riecken, K., Lamszus, K., Sievert, H., Pällmann, N., Bokemeyer, C., Hauber, J., Braig, M., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0043468 · Cited by 62 · see citing works
Targeting mutant p53: a key player in breast cancer pathogenesis and beyond
Qayoom, H., Haq, B. U., Sofi, S., Jan, N., Jan, A., & Mir, M. A. (2024) · Cell Communication and Signaling · doi:10.1186/s12964-024-01863-9 · Cited by 66 · see citing works
Shikonin Reduces Growth of Docetaxel-Resistant Prostate Cancer Cells Mainly through Necroptosis
Markowitsch, S. D., Juetter, K. M., Schupp, P., Hauschulte, K., Vakhrusheva, O., Slade, K. S., Thomas, A., Tsaur, I., Cinatl, J. J., Michaelis, M., et al. (2021) · Cancers · doi:10.3390/cancers13040882 · Cited by 59 · see citing works
Self-citationJones, R. J., Bjorklund, C. C., Baladandayuthapani, V., Kuhn, D. J., & Orlowski, R. Z. (2012) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-12-0135 · Cited by 59 · see citing works
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Feeley, K. P., Adams, C. M., Mitra, R., & Eischen, C. M. (2017) · Cancer Research · doi:10.1158/0008-5472.can-17-0809 · Cited by 57 · see citing works
Vallo, S., Michaelis, M., Rothweiler, F., Bartsch, G. C., Gust, K. M., Limbart, D. M., Rödel, F., Wezel, F., Haferkamp, A., & Cinatl, J. J. (2015) · Translational Oncology · doi:10.1016/j.tranon.2015.04.002 · Cited by 58 · see citing works
Self-citationCornillie, J., Wozniak, A., Li, H., Gebreyohannes, Y. K., Wellens, J., Hompes, D., Debiec-Rychter, M., Sciot, R., & Schöffski, P. (2020) · Clinical and Translational Oncology · doi:10.1007/s12094-019-02158-z · Cited by 56 · see citing works
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Weisberg, E., Halilovic, E., Cooke, V. G., Nonami, A., Ren, T., Sanda, T., Simkin, I., Yuan, J., Antonakos, B., Barys, L., et al. (2015) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-15-0429 · Cited by 56 · see citing works
Afonso, J., Gonçalves, C. S., Costa, M. F., Ferreira, D., Santos, L. L., Longatto‐Filho, A., & Baltazar, F. (2023) · Cancers · doi:10.3390/cancers15030982 · Cited by 54 · see citing works
Hoffman-Luca, C. G., Ziazadeh, D., McEachern, D., Zhao, Y., Sun, W., Debussche, L., & Wang, S. (2015) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-14-2506 · Cited by 52 · see citing works
Jamal, S. M. E., AlAmodi, A. A., Wahl, R. U., Grada, Z., Shareef, M. A., Hassan, S.-Y., Murad, F. G., Hassan, S.-L., Santourlidis, S., Gómez, C. R., et al. (2020) · Oncogene · doi:10.1038/s41388-020-1373-6 · Cited by 52 · see citing works
Aurora Kinases as Targets in Drug-Resistant Neuroblastoma Cells
Michaelis, M., Selt, F., Rothweiler, F., Löschmann, N., Nüsse, B., Dirks, W. G., Zehner, R., & Cinatl, J. J. (2014) · PLoS ONE · doi:10.1371/journal.pone.0108758 · Cited by 52 · see citing works
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Cell death-based treatment of neuroblastoma
Valter, K., Zhivotovsky, B., & Gogvadze, V. G. (2018) · Cell Death and Disease · doi:10.1038/s41419-017-0060-1 · Cited by 52 · see citing works
miR-20a enhances cisplatin resistance of human gastric cancer cell line by targeting NFKBIB
Du, Y., Zhu, M., Xin Min, Z. H. O. U., Huang, Z., Zhu, J., Xu, J., Cheng, G., Shu, Y., Liu, P., Zhu, W., et al. (2015) · Tumor Biology · doi:10.1007/s13277-015-3921-1 · Cited by 50 · see citing works
Liang, Y. Y., Bacanu, S., Sreekumar, L., Ramos, A. D., Dai, L., Michaelis, M., Cinatl, J. J., Seki, T., Cao, Y., Coffill, C. R., et al. (2021) · Cell chemical biology · doi:10.1016/j.chembiol.2021.06.007 · Cited by 49 · see citing works
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Crane, E. K., Kwan, S.-Y., Izaguirre, D. I., Tsang, Y. T. M., Mullany, L. K., Zu, Z., Richards, J. S., Gershenson, D. M., & Wong, K. (2015) · PLoS ONE · doi:10.1371/journal.pone.0135101 · Cited by 48 · see citing works
Zhang, Z., Kong, Y., Yang, W., Ma, F., Zhang, Y., Ji, S., Ma, E.-M., Liu, H., Chen, Y., & Hua, Y. (2016) · Oncology Reports · doi:10.3892/or.2016.5016 · Cited by 48 · see citing works
Pharmacologic activation of wild-type p53 by nutlin therapy in childhood cancer
Maerken, T. V., Rihani, A., Goethem, A. V., Paepe, A. D., Speleman, F., & Vandesompele, J. (2013) · Cancer Letters · doi:10.1016/j.canlet.2013.11.002 · Cited by 47 · see citing works
Kocik, J., Machula, M., Wisniewska, A., Surmiak, E., Holak, T. A., & Skalniak, L. (2019) · Cancers · doi:10.3390/cancers11071014 · Cited by 46 · see citing works
MDM2-p53 Interaction in Paediatric Solid Tumours: Preclinical Rationale, Biomarkers and Resistance
Barone, G., Tweddle, D. A., Shohet, J. M., Chesler, L., Moreno, L., Pearson, A. D. J., & Maerken, T. V. (2014) · Current Drug Targets · doi:10.2174/13894501113149990194 · Cited by 45 · see citing works
Voges, Y., Michaelis, M., Rothweiler, F., Schaller, T., Schneider, C., Politt, K., Mernberger, M., Nist, A., Stiewe, T., Wass, M. N., et al. (2016) · Cell Death and Disease · doi:10.1038/cddis.2016.257 · Cited by 46 · see citing works
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Bressy, C., Hastie, E. L., & Grdzelishvili, V. Z. (2017) · Molecular Therapy — Oncolytics · doi:10.1016/j.omto.2017.03.002 · Cited by 46 · see citing works
A therapeutic patent overview of MDM2/X-targeted therapies (2014–2018)
Skalniak, Ł., Surmiak, E., & Holak, T. A. (2019) · Expert Opinion on Therapeutic Patents · doi:10.1080/13543776.2019.1582645 · Cited by 45 · see citing works
Koyama, T., Shimizu, T., Kojima, Y., Sudo, K., Okuma, H. S., Shimoi, T., Ichikawa, H., Kohsaka, S., Sadachi, R., Hirakawa, A., et al. (2023) · Cancer Discovery · doi:10.1158/2159-8290.cd-23-0419 · Cited by 46 · see citing works
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Chen, L., & Tweddle, D. A. (2012) · Frontiers in Oncology · doi:10.3389/fonc.2012.00173 · Cited by 43 · see citing works
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Michaelis, M., Wass, M. N., & Cinatl, J. J. (2019) · Cancer Drug Resistance · doi:10.20517/cdr.2019.005 · Cited by 43 · see citing works
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Jochemsen, A. G. (2013) · Current Opinion in Oncology · doi:10.1097/cco.0000000000000033 · Cited by 42 · see citing works
Nutlin-3 sensitizes nasopharyngeal carcinoma cells to cisplatin-induced cytotoxicity
VOON, Y.-L., Ahmad, M., Wong, P., Husaini, R., Ng, W., Leong, C., Lane, D. P., & Khoo, A. S. B. (2015) · Oncology Reports · doi:10.3892/or.2015.4177 · Cited by 42 · see citing works
Tumor suppressor WWOX binds to ΔNp63α and sensitizes cancer cells to chemotherapy
Salah, Z., Bar-Mag, T., Kohn, Y., Pichiorri, F., Palumbo, T., Melino, G., & Aqeilan, R. I. (2013) · Cell Death and Disease · doi:10.1038/cddis.2013.6 · Cited by 41 · see citing works
Chen, Y., Zhang, Y., Song, W., Zhang, Y., Xiu, D., & Tan, M. (2019) · Anti-Cancer Agents in Medicinal Chemistry · doi:10.2174/1871520619666191209091230 · Cited by 40 · see citing works
Key Players of Cisplatin Resistance: Towards a Systems Pharmacology Approach
Sarin, N., Engel, F., Rothweiler, F., Cinatl, J. J., Michaelis, M., Frötschl, R., Fröhlich, H., & Kalayda, G. V. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19030767 · Cited by 39 · see citing works
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Li, C., & Xiao, Z. J. (2014) · BioMed Research International · doi:10.1155/2014/175721 · Cited by 36 · see citing works
Dual targeting of MDM2 and BCL2 as a therapeutic strategy in neuroblastoma
Goethem, A. V., Yigit, N., Moreno‐Smith, M., Vasudevan, S. A., Barbieri, E., Speleman, F., Shohet, J. M., Vandesompele, J., & Maerken, T. V. (2017) · Oncotarget · doi:10.18632/oncotarget.18982 · Cited by 36 · see citing works
Hata, A. N., Rowley, S. C., Archibald, H. L., Gomez‐Caraballo, M., Siddiqui, F. M., Ji, F., Jung, J., Light, M. E., Lee, J. S., Debüssche, L., et al. (2017) · Oncogene · doi:10.1038/onc.2017.258 · Cited by 34 · see citing works
Artesunate Inhibits the Growth Behavior of Docetaxel-Resistant Prostate Cancer Cells
Vakhrusheva, O., Erb, H. H. H., Braeunig, V., Markowitsch, S. D., Schupp, P., Baer, P. C., Slade, K. S., Thomas, A., Tsaur, I., Puhr, M., et al. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.789284 · Cited by 33 · see citing works
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Kucab, J. E., Hollstein, M. C., Arlt, V. M., & Phillips, D. H. (2016) · International Journal of Cancer · doi:10.1002/ijc.30504 · Cited by 31 · see citing works
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Self-citationDong, P., Ihira, K., Hamada, J., Watari, H., Yamada, T., Hosaka, M., Hanley, S. J. B., 工藤, 正., & Sakuragi, N. (2015) · Oncotarget · doi:10.18632/oncotarget.4847 · Cited by 30 · see citing works
Zanjirband, M., & Rahgozar, S. (2019) · Current Drug Targets · doi:10.2174/1389450120666190402120701 · Cited by 29 · see citing works
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Marcellino, B. K., Farnoud, N. R., Cassinat, B., Lü, M., Verger, E., McGovern, E. M., Patel, M. A., Medina-Martinez, J. S., Levine, M. F., Ossa, J. A., et al. (2020) · Blood Advances · doi:10.1182/bloodadvances.2020002379 · Cited by 29 · see citing works
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Resistance to nanoparticle albumin-bound paclitaxel is mediated by ABCB1 in urothelial cancer cells
Vallo, S., Köpp, R., Michaelis, M., Rothweiler, F., Bartsch, G. C., Brandt, M. P., Gust, K. M., Wezel, F., Blaheta, R. A., Haferkamp, A., et al. (2017) · Oncology Letters · doi:10.3892/ol.2017.5986 · Cited by 28 · see citing works
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Stepanenko, A. A., & KAVSAN, V. M. (2012) · Biopolymers and Cell · doi:10.7124/bc.000059 · Cited by 26 · see citing works
Petroni, M., Veschi, V., Gulino, A., & Giannini, G. (2012) · Frontiers in Oncology · doi:10.3389/fonc.2012.00141 · Cited by 25 · see citing works
p53, stem cell biology and childhood blastomas
Oh, L., Hafsi, H., Hainaut, P. L., & Ariffin, H. (2019) · Current Opinion in Oncology · doi:10.1097/cco.0000000000000504 · Cited by 23 · see citing works
Saafan, H., Foerster, S., Parra-Guillen, Z. P., Hammer, E., Michaelis, M., Cinatl, J. J., Völker, U., Fröhlich, H., Kloft, C., & Ritter, C. A. (2016) · European Journal of Pharmaceutical Sciences · doi:10.1016/j.ejps.2016.04.025 · Cited by 23 · see citing works
Self-citationMichaelis, M., Rothweiler, F., Agha, B., Barth, S., Voges, Y., Löschmann, N., von Deimling, A., Rainer Breitling, A., Doerr, H. W., Rödel, F., et al. (2012) · Cell Death and Disease · doi:10.1038/cddis.2012.35 · Cited by 22 · see citing works
Self-citationDrummond, C. J., Esfandiari, A., Liu, J., Lü, X., Hutton, C., Jackson, J., Bennaceur, K., Xu, Q., Makimanejavali, A. R., Bello, F. D., et al. (2016) · Oncotarget · doi:10.18632/oncotarget.10073 · Cited by 22 · see citing works
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Huang, Y., Wang, L., Zhou, Y., Bai, J., Li, N., Su, Z., & Cheng, X. (2025) · Cells · doi:10.3390/cells14080583 · Cited by 23 · see citing works
Protecting the genome from mdm2 and mdmx
Melo, A. N., & Eischen, C. M. (2012) · Genes & Cancer · doi:10.1177/1947601912454139 · Cited by 20 · see citing works
MDM2 inhibitors in cancer immunotherapy: Current status and perspective
Zeng, Q., Zeng, S., Dai, X., Ding, Y., Huang, C., Ruan, R., Xiong, J., Tang, X., & Deng, J. (2024) · Genes & Diseases · doi:10.1016/j.gendis.2024.101279 · Cited by 20 · see citing works
Wu, Y., Fu, Y., Zheng, L., Lin, G., Ma, J., Lou, J.-S., Zhu, H., He, Q., & Yang, B. (2013) · Cancer Letters · doi:10.1016/j.canlet.2013.08.039 · Cited by 20 · see citing works
Structure and function of MDM2 and MDM4 in health and disease
Zhu, I. Y., Lloyd, A., Critchley, W. R., Saikia, Q., Jade, D., Divan, A., Zeqiraj, E., Harrison, M. A., Brown, C. J., & Ponnambalam, S. (2025) · Biochemical Journal · doi:10.1042/bcj20240757 · Cited by 21 · see citing works
Towards image-based cancer cell lines authentication using deep neural networks
Mzurikwao, D., Khan, M. U., Samuel, O. W., Cinatl, J. J., Wass, M. N., Michaelis, M., Marcelli, G., & Ang, C. S. (2020) · Scientific Reports · doi:10.1038/s41598-020-76670-6 · Cited by 19 · see citing works
Self-citationSchilling, D., Düwel, M., Molls, M., & Multhoff, G. (2012) · Cell Stress and Chaperones · doi:10.1007/s12192-012-0369-8 · Cited by 19 · see citing works
Rothenburger, T., Thomas, D., Schreiber, Y., Wratil, P. R., Pflantz, T., Knecht, K. M., Digianantonio, K., Temple, J. E., Schneider, C., Baldauf, H., et al. (2021) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-021-02093-4 · Cited by 18 · see citing works
Self-citation
- Authors
- Michaelis, M., Rothweiler, F., Barth, S., Cinatl, J., van Rikxoort, M., Löschmann, N., Voges, Y., Breitling, R., von Deimling, A., Rödel, F., Weber, K., Fehse, B., Mack, E., Stiewe, T., Doerr, H. W., Speidel, D., & Cinatl, J.
- Affiliations
- Goethe University Frankfurt (DE)
- University Medical Center Hamburg-Eppendorf (DE)
- Philipps University of Marburg (DE)
- The University of Sydney (AU)
- Venue
- Cell Death & Disease
- Published
- 2011-12-15
- Volume
- 2
- Issue
- 12
- Pages
- e243-e243
- ISSN
- 2041-4889 (ISSN-L)
- PMC
- PMC3252738
- OpenAlex
- W2154563079
- Cited by
- 190
- References
- 40
- Citations by year
- 2026: 2 · 2025: 10 · 2024: 7 · 2023: 9 · 2022: 10 · 2021: 27 · 2020: 12 · 2019: 18 · 2018: 6 · 2017: 12 · 2016: 17 · 2015: 16 · 2014: 19 · 2013: 14 · 2012: 11
- FWCI
- 6.92
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by-nc-sa
- www.springer.com/tdm (unspecified)
- Locations
- Cell Death and Disease (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (submittedVersion)
- Kent Academic Repository (University of Kent) (submittedVersion)
- Publication Server of Goethe University Frankfurt am Main (Goethe University Frankfurt) (submittedVersion, cc-by-nc-sa)
- Research Explorer (The University of Manchester) (submittedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, cc-by)
- Funders
- Elekta
- Topics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Keywords
- Nutlin-3, MDM2 inhibitors, TP53 mutation, multidrug resistance, neuroblastoma, rhabdomyosarcoma, melanoma, radioresistance (biology), cisplatin resistance, doxorubicin resistance, vincristine resistance
- MeSH terms
- Adaptation, Biological, Antineoplastic Agents, Humans, Imidazoles, Mutation, Piperazines, Tumor Cells, Cultured, Tumor Suppressor Protein p53, Drug Resistance, Neoplasm, RNA Interference, Proto-Oncogene Proteins c-mdm2, Caspase 3, Caspase 7
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