TP53 mutations in cancer: Molecular features and therapeutic opportunities (Review)
- Authors:
- Maria Lina Tornesello
-
Affiliations: Molecular Biology and Viral Oncology Unit, Istituto Nazionale Tumori IRCCS Fondazione G. Pascale, I-80131 Napoli, Italy - Published online on: October 24, 2024 https://doi.org/10.3892/ijmm.2024.5448
- Article Number: 7
-
Copyright: © Tornesello . This is an open access article distributed under the terms of Creative Commons Attribution License.
This article is mentioned in:
Abstract
Lane DP and Crawford LV: T antigen is bound to a host protein in SV40-transformed cells. Nature. 278:261–263. 1979. View Article : Google Scholar : PubMed/NCBI | |
Linzer DI and Levine AJ: Characterization of a 54K dalton cellular SV40 tumor antigen present in SV40-transformed cells and uninfected embryonal carcinoma cells. Cell. 17:43–52. 1979. View Article : Google Scholar : PubMed/NCBI | |
Levine AJ and Oren M: The first 30 years of p53: Growing ever more complex. Nat Rev Cancer. 9:749–758. 2009. View Article : Google Scholar : PubMed/NCBI | |
Tornesello ML, Annunziata C, Tornesello AL, Buonaguro L and Buonaguro FM: Human Oncoviruses and p53 tumor suppressor pathway deregulation at the origin of human cancers. Cancers (Basel). 10:2132018. View Article : Google Scholar : PubMed/NCBI | |
Rotter V: p53, a transformation-related cellular-encoded protein, can be used as a biochemical marker for the detection of primary mouse tumor cells. Proc Natl Acad Sci USA. 80:2613–2617. 1983. View Article : Google Scholar : PubMed/NCBI | |
Oren M and Levine AJ: Molecular cloning of a cDNA specific for the murine p53 cellular tumor antigen. Proc Natl Acad Sci USA. 80:56–59. 1983. View Article : Google Scholar : PubMed/NCBI | |
Jenkins JR, Rudge K and Currie GA: Cellular immortalization by a cDNA clone encoding the transformation-associated phosphoprotein p53. Nature. 312:651–654. 1984. View Article : Google Scholar : PubMed/NCBI | |
Eliyahu D, Michalovitz D and Oren M: Overproduction of p53 antigen makes established cells highly tumorigenic. Nature. 316:158–160. 1985. View Article : Google Scholar : PubMed/NCBI | |
Finlay CA, Hinds PW, Tan TH, Eliyahu D, Oren M and Levine AJ: Activating mutations for transformation by p53 produce a gene product that forms an hsc70-p53 complex with an altered half-life. Mol Cell Biol. 8:531–539. 1988.PubMed/NCBI | |
Baker SJ, Fearon ER, Nigro JM, Hamilton SR, Preisinger AC, Jessup JM, vanTuinen P, Ledbetter DH, Barker DF, Nakamura Y, et al: Chromosome 17 deletions and p53 gene mutations in colorectal carcinomas. Science. 244:217–221. 1989. View Article : Google Scholar : PubMed/NCBI | |
Eliyahu D, Michalovitz D, Eliyahu S, Pinhasi-Kimhi O and Oren M: Wild-type p53 can inhibit oncogene-mediated focus formation. Proc Natl Acad Sci USA. 86:8763–8767. 1989. View Article : Google Scholar : PubMed/NCBI | |
Finlay CA, Hinds PW and Levine AJ: The p53 proto-oncogene can act as a suppressor of transformation. Cell. 57:1083–1093. 1989. View Article : Google Scholar : PubMed/NCBI | |
Schneider K, Zelley K, Nichols KE and Garber J: Li-Fraumeni Syndrome. GeneReviews(®). Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW and Amemiya A: University of Washington; Seattle, WA: 1993 | |
Fortuno C, Feng BJ, Carroll C, Innella G, Kohlmann W, Lázaro C, Br unet J, Feliubadaló L, Iglesias S, Menéndez M, et al: Cancer risks associated with TP53 pathogenic variants: Maximum likelihood analysis of extended pedigrees for diagnosis of first cancers beyond the Li-Fraumeni Syndrome Spectrum. JCO Precis Oncol. 8:e23004532024. View Article : Google Scholar : PubMed/NCBI | |
Malkin D: Li-fraumeni syndrome. Genes Cancer. 2:475–484. 2011. View Article : Google Scholar : PubMed/NCBI | |
Levine AJ: p53: 800 million years of evolution and 40 years of discovery. Nat Rev Cancer. 20:471–480. 2020. View Article : Google Scholar : PubMed/NCBI | |
Liu Y, Su Z, Tavana O and Gu W: Understanding the complexity of p53 in a new era of tumor suppression. Cancer Cell. 42:946–967. 2024. View Article : Google Scholar : PubMed/NCBI | |
Wang H, Guo M, Wei H and Chen Y: Targeting p53 pathways: Mechanisms, structures, and advances in therapy. Signal Transduct Target Ther. 8:922023. View Article : Google Scholar : PubMed/NCBI | |
Indeglia A and Murphy ME: Elucidating the chain of command: Our current understanding of critical target genes for p53-mediated tumor suppression. Crit Rev Biochem Mol Biol. 59:128–138. 2024. View Article : Google Scholar : PubMed/NCBI | |
Hanahan D and Weinberg RA: Hallmarks of cancer: The next generation. Cell. 144:646–674. 2011. View Article : Google Scholar : PubMed/NCBI | |
Olivier M, Hussain SP, Caron de Fromentel C, Hainaut P and Harris CC: TP53 mutation spectra and load: A tool for generating hypotheses on the etiology of cancer. IARC Sci Publ. (157): 247–270. 2004.PubMed/NCBI | |
Tornesello ML, Buonaguro L, Tatangelo F, Botti G, Izzo F and Buonaguro FM: Mutations in TP53, CTNNB1 and PIK3CA genes in hepatocellular carcinoma associated with hepatitis B and hepatitis C virus infections. Genomics. 102:74–83. 2013. View Article : Google Scholar : PubMed/NCBI | |
Hainaut P and Pfeifer GP: Somatic TP53 Mutations in the Era of Genome Sequencing. Cold Spring Harb Perspect Med. 6:a0261792016. View Article : Google Scholar : PubMed/NCBI | |
Sammons MA, Nguyen TT, McDade SS and Fischer M: Tumor suppressor p53: From engaging DNA to target gene regulation. Nucleic Acids Res. 48:8848–8869. 2020. View Article : Google Scholar : PubMed/NCBI | |
Kubbutat MH, Jones SN and Vousden KH: Regulation of p53 stability by Mdm2. Nature. 387:299–303. 1997. View Article : Google Scholar : PubMed/NCBI | |
Haupt Y, Maya R, Kazaz A and Oren M: Mdm2 promotes the rapid degradation of p53. Nature. 387:296–299. 1997. View Article : Google Scholar : PubMed/NCBI | |
Raj N and Attardi LD: The Transactivation Domains of the p53 Protein. Cold Spring Harb Perspect Med. 7:a0260472017. View Article : Google Scholar | |
Krois AS, Park S, Martinez-Yamout MA, Dyson HJ and Wright PE: Mapping Interactions of the Intrinsically Disordered C-Terminal Regions of Tetrameric p53 by Segmental Isotope Labeling and NMR. Biochemistry. 61:2709–2719. 2022. View Article : Google Scholar : PubMed/NCBI | |
Kruse JP and Gu W: SnapShot: p53 posttranslational modifications. Cell. 133:930–930.e1. 2008. View Article : Google Scholar : PubMed/NCBI | |
Brady CA, Jiang D, Mello SS, Johnson TM, Jarvis LA, Kozak MM, Kenzelmann Broz D, Basak S, Park EJ, McLaughlin ME, et al: Distinct p53 transcriptional programs dictate acute DNA-damage responses and tumor suppression. Cell. 145:571–583. 2011. View Article : Google Scholar : PubMed/NCBI | |
Riley T, Sontag E, Chen P and Levine A: Transcriptional control of human p53-regulated genes. Nat Rev Mol Cell Biol. 9:402–412. 2008. View Article : Google Scholar : PubMed/NCBI | |
el-Deiry WS, Kern SE, Pietenpol JA, Kinzler KW and Vogelstein B: Definition of a consensus binding site for p53. Nat Genet. 1:45–49. 1992. View Article : Google Scholar : PubMed/NCBI | |
Halazonetis TD and Kandil AN: Conformational shifts propagate from the oligomerization domain of p53 to its tetrameric DNA binding domain and restore DNA binding to select p53 mutants. EMBO J. 12:5057–5064. 1993. View Article : Google Scholar : PubMed/NCBI | |
Gu W and Roeder RG: Activation of p53 sequence-specific DNA binding by acetylation of the p53 C-terminal domain. Cell. 90:595–606. 1997. View Article : Google Scholar : PubMed/NCBI | |
Hernández Borrero LJ and El-Deiry WS: Tumor suppressor p53: Biology, signaling pathways, and therapeutic targeting. Biochim Biophys Acta Rev Cancer. 1876:1885562021. View Article : Google Scholar : PubMed/NCBI | |
Jenkins LM, Durell SR, Mazur SJ and Appella E: p53 N-terminal phosphorylation: A defining layer of complex regulation. Carcinogenesis. 33:1441–1449. 2012. View Article : Google Scholar : PubMed/NCBI | |
Lill NL, Grossman SR, Ginsberg D, DeCaprio J and Livingston DM: Binding and modulation of p53 by p300/CBP coactivators. Nature. 387:823–827. 1997. View Article : Google Scholar : PubMed/NCBI | |
Gostissa M, Hengstermann A, Fogal V, Sandy P, Schwarz SE, Scheffner M and Del Sal G: Activation of p53 by conjugation to the ubiquitin-like protein SUMO-1. EMBO J. 18:6462–6471. 1999. View Article : Google Scholar : PubMed/NCBI | |
Stindt MH, Carter S, Vigneron AM, Ryan KM and Vousden KH: MDM2 promotes SUMO-2/3 modification of p53 to modulate transcriptional activity. Cell Cycle. 10:3176–3188. 2011. View Article : Google Scholar : PubMed/NCBI | |
West LE and Gozani O: Regulation of p53 function by lysine methylation. Epigenomics. 3:361–369. 2011. View Article : Google Scholar : PubMed/NCBI | |
Laptenko O, Shiff I, Freed-Pastor W, Zupnick A, Mattia M, Freulich E, Shamir I, Kadouri N, Kahan T, Manfredi J, et al: The p53 C terminus controls site-specific DNA binding and promotes structural changes within the central DNA binding domain. Mol Cell. 57:1034–1046. 2015. View Article : Google Scholar : PubMed/NCBI | |
Shirangi TR, Zaika A and Moll UM: Nuclear degradation of p53 occurs during down-regulation of the p53 response after DNA damage. FASEB J. 16:420–422. 2002. View Article : Google Scholar : PubMed/NCBI | |
Zhu G, Pan C, Bei JX, Li B, Liang C, Xu Y and Fu X: Mutant p53 in cancer progression and targeted therapies. Front Oncol. 10:5951872020. View Article : Google Scholar : PubMed/NCBI | |
Donehower LA, Soussi T, Korkut A, Liu Y, Schultz A, Cardenas M, Li X, Babur O, Hsu TK, Lichtarge O, et al: Integrated Analysis of TP53 gene and pathway alterations in the cancer genome atlas. Cell Rep. 28:1370–1384 e5. 2019. View Article : Google Scholar : PubMed/NCBI | |
Chen X, Zhang T, Su W, Dou Z, Zhao D, Jin X, Lei H, Wang J, Xie X, Cheng B, et al: Mutant p53 in cancer: From molecular mechanism to therapeutic modulation. Cell Death Dis. 13:9742022. View Article : Google Scholar : PubMed/NCBI | |
Shirole NH, Pal D, Kastenhuber ER, Senturk S, Boroda J, Pisterzi P, Miller M, Munoz G, Anderluh M, Ladanyi M, et al: TP53 exon-6 truncating mutations produce separation of function isoforms with pro-tumorigenic functions. Elife. 5:e179292016. View Article : Google Scholar : PubMed/NCBI | |
Castrogiovanni C, Waterschoot B, De Backer O and Dumont P: Serine 392 phosphorylation modulates p53 mitochondrial translocation and transcription-independent apoptosis. Cell Death Differ. 25:190–203. 2018. View Article : Google Scholar : | |
Sonego M, Schiappacassi M, Lovisa S, Dall'Acqua A, Bagnoli M, Lovat F, Libra M, D'Andrea S, Canzonieri V, Militello L, et al: Stathmin regulates mutant p53 stability and transcriptional activity in ovarian cancer. EMBO Mol Med. 5:707–722. 2013. View Article : Google Scholar : PubMed/NCBI | |
Wang D, Nakayama M, Hong CP, Oshima H and Oshima M: Gain-of-Function p53 mutation acts as a genetic switch for TGFβ signaling-induced epithelial-to-mesenchymal transition in intestinal tumors. Cancer Res. 84:56–68. 2024. View Article : Google Scholar | |
Alvarado-Ortiz E, de la Cruz-López KG, Becerril-Rico J, Sarabia-Sánchez MA, Ortiz-Sánchez E and García-Carrancá A: Mutant p53 Gain-of-Function: Role in cancer development, progression, and therapeutic approaches. Front Cell Dev Biol. 8:6076702021. View Article : Google Scholar : PubMed/NCBI | |
Kastenhuber ER and Lowe SW: Putting p53 in Context. Cell. 170:1062–1078. 2017. View Article : Google Scholar : PubMed/NCBI | |
Boettcher S, Miller PG, Sharma R, McConkey M, Leventhal M, Krivtsov AV, Giacomelli AO, Wong W, Kim J, Chao S, et al: A dominant-negative effect drives selection of TP53 missense mutations in myeloid malignancies. Science. 365:599–604. 2019. View Article : Google Scholar : PubMed/NCBI | |
Aubrey BJ, Janic A, Chen Y, Chang C, Lieschke EC, Diepstraten ST, Kueh AJ, Bernardini JP, Dewson G, O'Reilly LA, et al: Mutant TRP53 exerts a target gene-selective dominant-negative effect to drive tumor development. Genes Dev. 32:1420–1429. 2018. View Article : Google Scholar : PubMed/NCBI | |
Martins CP, Brown-Swigart L and Evan GI: Modeling the therapeutic efficacy of p53 restoration in tumors. Cell. 127:1323–1334. 2006. View Article : Google Scholar : PubMed/NCBI | |
Shchors K, Persson AI, Rostker F, Tihan T, Lyubynska N, Li N, Swigart LB, Berger MS, Hanahan D, Weiss WA and Evan GI: Using a preclinical mouse model of high-grade astrocytoma to optimize p53 restoration therapy. Proc Natl Acad Sci USA. 110:E1480–E1489. 2013. View Article : Google Scholar : PubMed/NCBI | |
Ventura A, Kirsch DG, McLaughlin ME, Tuveson DA, Grimm J, Lintault L, Newman J, Reczek EE, Weissleder R and Jacks T: Restoration of p53 function leads to tumour regression in vivo. Nature. 445:661–665. 2007. View Article : Google Scholar : PubMed/NCBI | |
Baugh EH, Ke H, Levine AJ, Bonneau RA and Chan CS: Why are there hotspot mutations in the TP53 gene in human cancers? Cell Death Differ. 25:154–160. 2018. View Article : Google Scholar : | |
Yang C, Lou G and Jin WL: The arsenal of TP53 mutants therapies: Neoantigens and bispecific antibodies. Signal Transduct Target Ther. 6:2192021. View Article : Google Scholar : PubMed/NCBI | |
McCann JJ, Vasilevskaya IA, McNair C, Gallagher P, Neupane NP, de Leeuw R, Shafi AA, Dylgjeri E, Mandigo AC, Schiewer MJ and Knudsen KE: Mutant p53 elicits context-dependent pro-tumorigenic phenotypes. Oncogene. 41:444–458. 2022. View Article : Google Scholar : | |
Xiong S, Chachad D, Zhang Y, Gencel-Augusto J, Sirito M, Pant V, Yang P, Sun C, Chau G, Qi Y, et al: Differential Gain-of-Function Activity of Three p53 Hotspot mutants in vivo. Cancer Res. 82:1926–1936. 2022. View Article : Google Scholar : PubMed/NCBI | |
Rasquinha JA, Bej A, Dutta S and Mukherjee S: Intrinsic differences in backbone dynamics between wild type and DNA-Contact Mutants of the p53 DNA binding domain revealed by nuclear magnetic resonance spectroscopy. Biochemistry. 56:4962–4971. 2017. View Article : Google Scholar : PubMed/NCBI | |
Salari A, Thomay K, Lentes J, Ebersold J, Hagedorn M, Skawran B, Davenport C, Schambach A, Schlegelberger B and Göhring G: Effect of TP53 contact and conformational mutations on cell survival and erythropoiesis of human hematopoietic stem cells in a long term culture model. Oncotarget. 9:29869–29876. 2018. View Article : Google Scholar : PubMed/NCBI | |
Pfister NT and Prives C: Transcriptional regulation by wild-type and cancer-related mutant forms of p53. Cold Spring Harb Perspect Med. 7:a0260542017. View Article : Google Scholar | |
Di Agostino S, Strano S, Emiliozzi V, Zerbini V, Mottolese M, Sacchi A, Blandino G and Piaggio G: Gain of function of mutant p53: The mutant p53/NF-Y protein complex reveals an aberrant transcriptional mechanism of cell cycle regulation. Cancer Cell. 10:191–202. 2006. View Article : Google Scholar : PubMed/NCBI | |
Di Agostino S, Sorrentino G, Ingallina E, Valenti F, Ferraiuolo M, Bicciato S, Piazza S, Strano S, Del Sal G and Blandino G: YAP enhances the pro-proliferative transcriptional activity of mutant p53 proteins. EMBO Rep. 17:188–201. 2016. View Article : Google Scholar | |
Zhang J, Sun W, Kong X, Zhang Y, Yang HJ, Ren C, Jiang Y, Chen M and Chen X: Mutant p53 antagonizes p63/p73-mediated tumor suppression via Notch1. Proc Natl Acad Sci USA. 116:24259–24267. 2019. View Article : Google Scholar : PubMed/NCBI | |
Morselli E, Tasdemir E, Maiuri MC, Galluzzi L, Kepp O, Criollo A, Vicencio JM, Soussi T and Kroemer G: Mutant p53 protein localized in the cytoplasm inhibits autophagy. Cell Cycle. 7:3056–3061. 2008. View Article : Google Scholar : PubMed/NCBI | |
Wang Z, Burigotto M, Ghetti S, Vaillant F, Tan T, Capaldo BD, Palmieri M, Hirokawa Y, Tai L, Simpson DS, et al: Loss-of-Function but not gain-of-function properties of mutant TP53 are critical for the proliferation, survival, and metastasis of a broad range of cancer cells. Cancer Discov. 14:362–379. 2024. View Article : Google Scholar : | |
Roszkowska KA, Piecuch A, Sady M, Gajewski Z and Flis S: Gain of Function (GOF) Mutant p53 in cancer-current therapeutic approaches. Int J Mol Sci. 23:132872022. View Article : Google Scholar : PubMed/NCBI | |
Bougeard G, Sesboue R, Baert-Desurmont S, Martin C, Tinat J, Brugières L, Chompret A, de Paillerets BB, Stoppa-Lyonnet D, Bonaïti-Pellié C, et al: Molecular basis of the Li-Fraumeni syndrome: An update from the French LFS families. J Med Genet. 45:535–538. 2008. View Article : Google Scholar : PubMed/NCBI | |
Levine AJ: Spontaneous and inherited TP53 genetic alterations. Oncogene. 40:5975–5983. 2021. View Article : Google Scholar : PubMed/NCBI | |
Robles AI, Jen J and Harris CC: Clinical Outcomes of TP53 mutations in cancers. Cold Spring Harb Perspect Med. 6:a0262942016. View Article : Google Scholar : PubMed/NCBI | |
Sampath J, Sun D, Kidd VJ, Grenet J, Gandhi A, Shapiro LH, Wang Q, Zambetti GP and Schuetz JD: Mutant p53 cooperates with ETS and selectively up-regulates human MDR1 not MRP1. J Biol Chem. 276:39359–39367. 2001. View Article : Google Scholar : PubMed/NCBI | |
Bossi G, Lapi E, Strano S, Rinaldo C, Blandino G and Sacchi A: Mutant p53 gain of function: reduction of tumor malignancy of human cancer cell lines through abrogation of mutant p53 expression. Oncogene. 25:304–309. 2006. View Article : Google Scholar | |
Wang Q, Wei F, Lv G, Li C, Liu T, Hadjipanayis CG, Zhang G, Hao C and Bellail AC: The association of TP53 mutations with the resistance of colorectal carcinoma to the insulin-like growth factor-1 receptor inhibitor picropodophyllin. BMC Cancer. 13:5212013. View Article : Google Scholar : PubMed/NCBI | |
Wong RP, Tsang WP, Chau PY, Co NN, Tsang TY and Kwok TT: p53-R273H gains new function in induction of drug resistance through down-regulation of procaspase-3. Mol Cancer Ther. 6:1054–1061. 2007. View Article : Google Scholar : PubMed/NCBI | |
Huang Y, Liu N, Liu J, Liu Y, Zhang C, Long S, Luo G, Zhang L and Zhang Y: Mutant p53 drives cancer chemotherapy resistance due to loss of function on activating transcription of PUMA. Cell Cycle. 18:3442–3455. 2019. View Article : Google Scholar : PubMed/NCBI | |
O'Connor PM, Jackman J, Bae I, Myers TG, Fan S, Mutoh M, Scudiero DA, Monks A and Sausville EA: Characterization of the p53 tumor suppressor pathway in cell lines of the National Cancer Institute anticancer drug screen and correlations with the growth-inhibitory potency of 123 anticancer agents. Cancer Res. 57:4285–4300. 1997.PubMed/NCBI | |
Kong X, Yu D, Wang Z and Li S: Relationship between p53 status and the bioeffect of ionizing radiation. Oncol Lett. 22:6612021. View Article : Google Scholar : PubMed/NCBI | |
Hassin O and Oren M: Drugging p53 in cancer: One protein, many targets. Nat Rev Drug Discov. 22:127–144. 2023. View Article : Google Scholar | |
Peuget S, Zhou X and Selivanova G: Translating p53-based therapies for cancer into the clinic. Nat Rev Cancer. 24:192–215. 2024. View Article : Google Scholar : PubMed/NCBI | |
Hu J, Cao J, Topatana W, Juengpanich S, Li S, Zhang B, Shen J, Cai L, Cai X and Chen M: Targeting mutant p53 for cancer therapy: Direct and indirect strategies. J Hematol Oncol. 14:1572021. View Article : Google Scholar : PubMed/NCBI | |
Gu H, Wang X, Rao S, Wang J, Zhao J, Ren FL, Mu R, Yang Y, Qi Q, Liu W, et al: Gambogic acid mediates apoptosis as a p53 inducer through down-regulation of mdm2 in wild-type p53-expressing cancer cells. Mol Cancer Ther. 7:3298–3305. 2008. View Article : Google Scholar : PubMed/NCBI | |
Wang J, Zhao Q, Qi Q, Gu HY, Rong JJ, Mu R, Zou MJ, Tao L, You QD and Guo QL: Gambogic acid-induced degradation of mutant p53 is mediated by proteasome and related to CHIP. J Cell Biochem. 112:509–519. 2011. View Article : Google Scholar : PubMed/NCBI | |
Pan H, Lu LY, Wang XQ, Li BX, Kelly K and Lin HS: Gambogic acid induces cell apoptosis and inhibits MAPK Pathway in PTEN(-/-)/p53(-/-) prostate cancer cells in vitro and ex vivo. Chin J Integr Med. 24:109–116. 2018. View Article : Google Scholar | |
Garufi A, Pistritto G, Cirone M and D'Orazi G: Reactivation of mutant p53 by capsaicin, the major constituent of peppers. J Exp Clin Cancer Res. 35:1362016. View Article : Google Scholar : PubMed/NCBI | |
Padmanabhan A, Candelaria N, Wong KK, Nikolai BC, Lonard DM, O'Malley BW and Richards JS: USP15-dependent lysosomal pathway controls p53-R175H turnover in ovarian cancer cells. Nat Commun. 9:12702018. View Article : Google Scholar : PubMed/NCBI | |
Zhang S, Zhou L, Hong B, van den Heuvel AP, Prabhu VV, Warfel NA, Kline CL, Dicker DT, Kopelovich L and El-Deiry WS: Small-Molecule NSC59984 Restores p53 pathway signaling and antitumor effects against colorectal cancer via p73 activation and degradation of mutant p53. Cancer Res. 75:3842–3852. 2015. View Article : Google Scholar : PubMed/NCBI | |
Jhaveri K and Modi S: Ganetespib: Research and clinical development. Onco Targets Ther. 8:1849–1858. 2015.PubMed/NCBI | |
Alexandrova EM, Xu S and Moll UM: Ganetespib synergizes with cyclophosphamide to improve survival of mice with autochthonous tumors in a mutant p53-dependent manner. Cell Death Dis. 8:e26832017. View Article : Google Scholar : PubMed/NCBI | |
Wong WW, Dimitroulakos J, Minden MD and Penn LZ: HMG-CoA reductase inhibitors and the malignant cell: the statin family of drugs as triggers of tumor-specific apoptosis. Leukemia. 16:508–519. 2002. View Article : Google Scholar : PubMed/NCBI | |
Kornblau SM, Banker DE, Stirewalt D, Shen D, Lemker E, Verstovsek S, Estrov Z, Faderl S, Cortes J, Beran M, et al: Blockade of adaptive defensive changes in cholesterol uptake and synthesis in AML by the addition of pravastatin to idarubicin + high-dose Ara-C: A phase 1 study. Blood. 109:2999–3006. 2007. View Article : Google Scholar | |
Parrales A, Ranjan A, Iyer SV, Padhye S, Weir SJ, Roy A and Iwakuma T: DNAJA1 controls the fate of misfolded mutant p53 through the mevalonate pathway. Nat Cell Biol. 18:1233–1243. 2016. View Article : Google Scholar : PubMed/NCBI | |
Martirosyan A, Clendening JW, Goard CA and Penn LZ: Lovastatin induces apoptosis of ovarian cancer cells and synergizes with doxorubicin: Potential therapeutic relevance. BMC Cancer. 10:1032010. View Article : Google Scholar : PubMed/NCBI | |
Li D, Marchenko ND and Moll UM: SAHA shows preferential cytotoxicity in mutant p53 cancer cells by destabilizing mutant p53 through inhibition of the HDAC6-Hsp90 chaperone axis. Cell Death Differ. 18:1904–1913. 2011. View Article : Google Scholar : PubMed/NCBI | |
Durairaj G, Demir O, Lim B, Baronio R, Tifrea D, Hall LV, DeForest JC, Lauinger L, Jebril Fallatah MM, Yu C, et al: Discovery of compounds that reactivate p53 mutants in vitro and in vivo. Cell Chem Biol. 29:1381–1395 e13. 2022. View Article : Google Scholar | |
Di Agostino S, Fontemaggi G, Strano S, Blandino G and D'Orazi G: Targeting mutant p53 in cancer: The latest insights. J Exp Clin Cancer Res. 38:2902019. View Article : Google Scholar : PubMed/NCBI | |
Huang Y, Jiao Z, Fu Y, Hou Y, Sun J, Hu F, Yu S, Gong K, Liu Y and Zhao G: An overview of the functions of p53 and drugs acting either on wild- or mutant-type p53. Eur J Med Chem. 265:1161212024. View Article : Google Scholar : PubMed/NCBI | |
Bykov VJ, Issaeva N, Shilov A, Hultcrantz M, Pugacheva E, Chumakov P, Bergman J, Wiman KG and Selivanova G: Restoration of the tumor suppressor function to mutant p53 by a low-molecular-weight compound. Nat Med. 8:282–288. 2002. View Article : Google Scholar : PubMed/NCBI | |
Saha MN, Jiang H, Yang Y, Reece D and Chang H: PRIMA-1Met/APR-246 displays high antitumor activity in multiple myeloma by induction of p73 and Noxa. Mol Cancer Ther. 12:2331–2341. 2013. View Article : Google Scholar : PubMed/NCBI | |
Furukawa H, Makino T, Yamasaki M, Tanaka K, Miyazaki Y, Takahashi T, Kurokawa Y, Nakajima K, Takiguchi S, Mori M and Doki Y: PRIMA-1 induces p53-mediated apoptosis by upregulating Noxa in esophageal squamous cell carcinoma with TP53 missense mutation. Cancer Sci. 109:412–421. 2018. View Article : Google Scholar | |
Zandi R, Selivanova G, Christensen CL, Gerds TA, Willumsen BM and Poulsen HS: PRIMA-1Met/APR-246 induces apoptosis and tumor growth delay in small cell lung cancer expressing mutant p53. Clin Cancer Res. 17:2830–2841. 2011. View Article : Google Scholar : PubMed/NCBI | |
Li XL, Zhou J, Chan ZL, Chooi JY, Chen ZR and Chng WJ: PRIMA-1met (APR-246) inhibits growth of colorectal cancer cells with different p53 status through distinct mechanisms. Oncotarget. 6:36689–36699. 2015. View Article : Google Scholar : PubMed/NCBI | |
Sallman DA, DeZern AE, Garcia-Manero G, Steensma DP, Roboz GJ, Sekeres MA, Cluzeau T, Sweet KL, McLemore A, McGraw KL, et al: Eprenetapopt (APR-246) and Azacitidine in TP53-Mutant myelodysplastic syndromes. J Clin Oncol. 39:1584–1594. 2021. View Article : Google Scholar : PubMed/NCBI | |
Cluzeau T, Sebert M, Rahmé R, Cuzzubbo S, Lehmann-Che J, Madelaine I, Peterlin P, Bève B, Attalah H, Chermat F, et al: Eprenetapopt Plus Azacitidine in TP53-Mutated myelodysplastic syndromes and acute myeloid leukemia: A phase II study by the groupe francophone des myélodysplasies (GFM). J Clin Oncol. 39:1575–1583. 2021. View Article : Google Scholar : PubMed/NCBI | |
Grellety T, Laroche-Clary A, Chaire V, Lagarde P, Chibon F, Neuville A and Italiano A: PRIMA-1(MET) induces death in soft-tissue sarcomas cell independent of p53. BMC Cancer. 15:6842015. View Article : Google Scholar : PubMed/NCBI | |
Aggarwal M, Saxena R, Sinclair E, Fu Y, Jacobs A, Dyba M, Wang X, Cruz I, Berry D, Kallakury B, et al: Reactivation of mutant p53 by a dietary-related compound phenethyl isothiocyanate inhibits tumor growth. Cell Death Differ. 23:1615–1627. 2016. View Article : Google Scholar : PubMed/NCBI | |
Aggarwal M, Saxena R, Asif N, Sinclair E, Tan J, Cruz I, Berry D, Kallakury B, Pham Q, Wang TTY and Chung FL: p53 mutant-type in human prostate cancer cells determines the sensitivity to phenethyl isothiocyanate induced growth inhibition. J Exp Clin Cancer Res. 38:3072019. View Article : Google Scholar : PubMed/NCBI | |
Dumbrava ECJ, Tolcher ML, Shapiro AW, Thompson G, El-Khoueiry JA, Vandross AB, Kummar AL, Parikh S, Munster AR, Daly PM, et al: First-in-human study of PC14586, a small molecule structural corrector of Y220C mutant p53, in patients with advanced solid tumors harboring a TP53 Y220C mutation. J Clin Oncol. 40:12022. View Article : Google Scholar | |
Chen S, Wu JL, Liang Y, Tang YG, Song HX, Wu LL, Xing YF, Yan N, Li YT, Wang ZY, et al: Arsenic trioxide rescues structural p53 mutations through a cryptic allosteric site. Cancer Cell. 39:225–239.e8. 2021. View Article : Google Scholar | |
Tang Y, Song H, Wang Z, Xiao S, Xiang X, Zhan H, Wu L, Wu J, Xing Y, Tan Y, et al: Repurposing antiparasitic antimonials to noncovalently rescue temperature-sensitive p53 mutations. Cell Rep. 39:1106222022. View Article : Google Scholar : PubMed/NCBI | |
Lindemann A, Patel AA, Silver NL, Tang L, Liu Z, Wang L, Tanaka N, Rao X, Takahashi H, Maduka NK, et al: COTI-2, A novel thiosemicarbazone derivative, exhibits antitumor activity in HNSCC through p53-dependent and -independent Mechanisms. Clin Cancer Res. 25:5650–5662. 2019. View Article : Google Scholar : PubMed/NCBI | |
Issaeva N, Bozko P, Enge M, Protopopova M, Verhoef LG, Masucci M, Pramanik A and Selivanova G: Small molecule RITA binds to p53, blocks p53-HDM-2 interaction and activates p53 function in tumors. Nat Med. 10:1321–1328. 2004. View Article : Google Scholar : PubMed/NCBI | |
Zhao CY, Grinkevich VV, Nikulenkov F, Bao W and Selivanova G: Rescue of the apoptotic-inducing function of mutant p53 by small molecule RITA. Cell Cycle. 9:1847–1855. 2010. View Article : Google Scholar : PubMed/NCBI | |
Burmakin M, Shi Y, Hedström E, Kogner P and Selivanova G: Dual targeting of wild-type and mutant p53 by small molecule RITA results in the inhibition of N-Myc and key survival oncogenes and kills neuroblastoma cells in vivo and in vitro. Clin Cancer Res. 19:5092–5103. 2013. View Article : Google Scholar : PubMed/NCBI | |
Foster BA, Coffey HA, Morin MJ and Rastinejad F: Pharmacological rescue of mutant p53 conformation and function. Science. 286:2507–2510. 1999. View Article : Google Scholar | |
Takimoto R, Wang W, Dicker DT, Rastinejad F, Lyssikatos J and el-Deiry WS: The mutant p53-conformation modifying drug, CP-31398, can induce apoptosis of human cancer cells and can stabilize wild-type p53 protein. Cancer Biol Ther. 1:47–55. 2002. View Article : Google Scholar : PubMed/NCBI | |
Wang W, Takimoto R, Rastinejad F and El-Deiry WS: Stabilization of p53 by CP-31398 inhibits ubiquitination without altering phosphorylation at serine 15 or 20 or MDM2 binding. Mol Cell Biol. 23:2171–2181. 2003. View Article : Google Scholar : PubMed/NCBI | |
He XX, Zhang YN, Yan JW, Yan JJ, Wu Q and Song YH: CP-31398 inhibits the growth of p53-mutated liver cancer cells in vitro and in vivo. Tumour Biol. 37:807–815. 2016. View Article : Google Scholar | |
He X, Kong X, Yan J, Zhang Y, Wu Q, Chang Y, Shang H, Dou Q, Song Y and Liu F: CP-31398 prevents the growth of p53-mutated colorectal cancer cells in vitro and in vivo. Tumour Biol. 36:1437–1444. 2015. View Article : Google Scholar : PubMed/NCBI | |
Arihara Y, Takada K, Kamihara Y, Hayasaka N, Nakamura H, Murase K, Ikeda H, Iyama S, Sato T, Miyanishi K, et al: Small molecule CP-31398 induces reactive oxygen species-dependent apoptosis in human multiple myeloma. Oncotarget. 8:65889–65899. 2017. View Article : Google Scholar : PubMed/NCBI | |
Liu X, Wilcken R, Joerger AC, Chuckowree IS, Amin J, Spencer J and Fersht AR: Small molecule induced reactivation of mutant p53 in cancer cells. Nucleic Acids Res. 41:6034–6044. 2013. View Article : Google Scholar : PubMed/NCBI | |
Yu X, Vazquez A, Levine AJ and Carpizo DR: Allele-specific p53 mutant reactivation. Cancer Cell. 21:614–625. 2012. View Article : Google Scholar : PubMed/NCBI | |
Blanden AR, Yu X, Blayney AJ, Demas C, Ha JH, Liu Y, Withers T, Carpizo DR and Loh SN: Zinc shapes the folding landscape of p53 and establishes a pathway for reactivating structurally diverse cancer mutants. Elife. 9:e614872020. View Article : Google Scholar : PubMed/NCBI | |
Yu X, Blanden A, Tsang AT, Zaman S, Liu Y, Gilleran J, Bencivenga AF, Kimball SD, Loh SN and Carpizo DR: Thiosemicarbazones functioning as zinc metallochaperones to reactivate mutant p53. Mol Pharmacol. 91:567–575. 2017. View Article : Google Scholar : PubMed/NCBI | |
Alexandrova EM, Yallowitz AR, Li D, Xu S, Schulz R, Proia DA, Lozano G, Dobbelstein M and Moll UM: Improving survival by exploiting tumour dependence on stabilized mutant p53 for treatment. Nature. 523:352–356. 2015. View Article : Google Scholar : PubMed/NCBI | |
Shi XY, Ding W, Li TQ, Zhang YX and Zhao SC: Histone Deacetylase (HDAC) inhibitor, suberoylanilide hydroxamic acid (SAHA), induces apoptosis in prostate cancer cell lines via the Akt/FOXO3a signaling pathway. Med Sci Monit. 23:5793–5802. 2017. View Article : Google Scholar : PubMed/NCBI | |
Panicker J, Li Z, McMahon C, Sizer C, Steadman K, Piekarz R, Bates SE and Thiele CJ: Romidepsin (FK228/depsipeptide) controls growth and induces apoptosis in neuroblastoma tumor cells. Cell Cycle. 9:1830–1838. 2010. View Article : Google Scholar : PubMed/NCBI | |
Yu X, Guo ZS, Marcu MG, Neckers L, Nguyen DM, Chen GA and Schrump DS: Modulation of p53, ErbB1, ErbB2, and Raf-1 expression in lung cancer cells by depsipeptide FR901228. J Natl Cancer Inst. 94:504–513. 2002. View Article : Google Scholar : PubMed/NCBI | |
Lo YH, Kolahi KS, Du Y, Chang CY, Krokhotin A, Nair A, Sobba WD, Karlsson K, Jones SJ, Longacre TA, et al: A CRISPR/Cas9-Engineered ARID1A-Deficient human gastric cancer organoid model reveals essential and nonessential modes of oncogenic transformation. Cancer Discov. 11:1562–1581. 2021. View Article : Google Scholar : PubMed/NCBI | |
Geisinger JM and Stearns T: CRISPR/Cas9 treatment causes extended TP53-dependent cell cycle arrest in human cells. Nucleic Acids Res. 48:9067–9081. 2020. View Article : Google Scholar : PubMed/NCBI | |
Alvarez MM, Biayna J and Supek F: TP53-dependent toxicity of CRISPR/Cas9 cuts is differential across genomic loci and can confound genetic screening. Nat Commun. 13:45202022. View Article : Google Scholar : PubMed/NCBI | |
Hsiue EH, Wright KM, Douglass J, Hwang MS, Mog BJ, Pearlman AH, Paul S, DiNapoli SR, Konig MF, Wang Q, et al: Targeting a neoantigen derived from a common TP53 mutation. Science. 371:eabc86972021. View Article : Google Scholar : PubMed/NCBI | |
Wang Z, Strasser A and Kelly GL: Should mutant TP53 be targeted for cancer therapy? Cell Death Differ. 29:911–920. 2022. View Article : Google Scholar : PubMed/NCBI | |
Olivier M, Hollstein M and Hainaut P: TP53 mutations in human cancers: Origins, consequences, and clinical use. Cold Spring Harb Perspect Biol. 2:a0010082010. View Article : Google Scholar : PubMed/NCBI | |
Chatterjee K, Das P, Chattopadhyay NR, Mal S and Choudhuri T: The interplay between Epstein-Bar virus (EBV) with the p53 and its homologs during EBV associated malignancies. Heliyon. 5:e026242019. View Article : Google Scholar : PubMed/NCBI | |
Martinez-Zapien D, Ruiz FX, Poirson J, Mitschler A, Ramirez J, Forster A, Cousido-Siah A, Masson M, Vande Pol S, Podjarny A, et al: Structure of the E6/E6AP/p53 complex required for HPV-mediated degradation of p53. Nature. 529:541–545. 2016. View Article : Google Scholar : PubMed/NCBI | |
Lan KH, Sheu ML, Hwang SJ, Yen SH, Chen SY, Wu JC, Wang YJ, Kato N, Omata M, Chang FY and Lee SD: HCV NS5A interacts with p53 and inhibits p53-mediated apoptosis. Oncogene. 21:4801–4811. 2002. View Article : Google Scholar : PubMed/NCBI |