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p53-Hsp90 Axis in Human Cancer

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Heat Shock Protein 90 in Human Diseases and Disorders

Part of the book series: Heat Shock Proteins ((HESP,volume 19))

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Abstract

The heat shock protein 90 (Hsp90) is a ubiquitous molecular chaperone that is abundantly expressed in cancer cells and plays a pivotal role in correct folding and functions of a variety of oncogenic clients. Hsp90 is up-regulated in response to cellular stresses that cancer cells encounter, such as heat, hypoxia and nutrient deprivation, conditions commonly associated with the tumor microenvironment. P53 is the tumor suppressor gene that is mutated in nearly 50% of all human cancers. When mutated p53 not only lose its tumor suppressive function but also gain novel oncogenic activities via gain-of-function mechanisms leading to increased genomic instability, chemoresistance, and metastasis, which promote tumor progression. In contrast to wild-type p53, mutant p53 is protected from degradation via interaction with Hsp90 leading to marked stabilization of mutant p53 protein in cancer cells. Recent in vivo studies unequivocally have proven that the stabilization of mutant p53 is crucial pre-requisite for its oncogenic functions. The pharmacological targeting the pathways involved in the stabilization of mutant p53, in particular, the Hsp90 chaperone complex, recently attracted a lot of attention as a promising therapeutic approach to treat mutant p53 harboring cancers.

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Abbreviations

DN:

dominant negative

GOF:

gain-of-function

HDAC:

histone deacetylase

HSF1:

heat shock factor 1

HSP:

heat shock protein

LOH:

loss of heterozygosity

MDM2:

mouse double-minute 2

RTK:

receptor tyrosine kinases

SAHA:

suberoylanilide hydroxamic acid

References

  • Adorno M, Cordenonsi M, Montagner M et al (2009) A mutant-p53/Smad complex opposes p63 to empower TGFbeta-induced metastasis. Cell 137:87–98

    Article  CAS  PubMed  Google Scholar 

  • Alexandrova EM, Marchenko ND (2015) Mutant p53 – heat shock response oncogenic cooperation: a new mechanism of cancer cell survival. Front Endocrinol (Lausanne) 6:53

    Article  Google Scholar 

  • Alexandrova EM, Yallowitz AR, Li D et al (2015) Improving survival by exploiting tumour dependence on stabilized mutant p53 for treatment. Nature 523:352–356

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Alexandrova EM, Mirza SA, Xu S, Schulz-Heddergott R, Marchenko ND, Moll UM (2017a) p53 loss-of-heterozygosity is a necessary prerequisite for mutant p53 stabilization and gain-of-function in vivo. Cell Death Dis 8:e2661

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Alexandrova EM, Xu S, Moll UM (2017b) Ganetespib synergizes with cyclophosphamide to improve survival of mice with autochthonous tumors in a mutant p53-dependent manner. Cell Death Dis 8:e2683

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Barrott JJ, Haystead TA (2013) Hsp90, an unlikely ally in the war on cancer. FEBS J 280:1381–1396

    Article  CAS  PubMed  Google Scholar 

  • Baugh EH, Ke H, Levine AJ, Bonneau RA, Chan CS (2018) Why are there hotspot mutations in the TP53 gene in human cancers? Cell Death Differ 25:154–160

    Article  CAS  PubMed  Google Scholar 

  • Blagosklonny MV, Toretsky J, Bohen S, Neckers L (1996) Mutant conformation of p53 translated in vitro or in vivo requires functional Hsp90. Proc Natl Acad Sci USA 93:8379–8383

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Blandino G, Di Agostino S (2018) New therapeutic strategies to treat human cancers expressing mutant p53 proteins. J Exp Clin Cancer Res 37:30

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Bouaoun L, Sonkin D, Ardin M et al (2016) TP53 variations in human cancers: new lessons from the IARC TP53 database and genomics data. Hum Mutat 37:865–876

    Article  CAS  PubMed  Google Scholar 

  • Burkhart C, Fleyshman D, Kohrn R et al (2014) Curaxin CBL0137 eradicates drug resistant cancer stem cells and potentiates efficacy of gemcitabine in preclinical models of pancreatic cancer. Oncotarget 5:11038–11053

    Article  PubMed  PubMed Central  Google Scholar 

  • Butler LM, Ferraldeschi R, Armstrong HK, Centenera MM, Workman P (2015) Maximizing the therapeutic potential of Hsp90 inhibitors. Mol Cancer Res 13:1445–1451

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chatterjee S, Burns TF (2017) Targeting heat shock proteins in cancer: a promising therapeutic approach. Int J Mol Sci 18:1978

    Article  PubMed Central  CAS  Google Scholar 

  • Connell P, Ballinger CA, Jiang J et al (2001) The co-chaperone CHIP regulates protein triage decisions mediated by heat-shock proteins. Nat Cell Biol 3:93–96

    Article  CAS  PubMed  Google Scholar 

  • D’Amato V, Raimondo L, Formisano L et al (2015) Mechanisms of lapatinib resistance in HER2-driven breast cancer. Cancer Treat Rev 41:877–883

    Article  PubMed  CAS  Google Scholar 

  • Dai C, Whitesell L, Rogers AB, Lindquist S (2007) Heat shock factor 1 is a powerful multifaceted modifier of carcinogenesis. Cell 130:1005–1018

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dai C, Santagata S, Tang Z et al (2012) Loss of tumor suppressor NF1 activates HSF1 to promote carcinogenesis. J Clin Invest 122:3742–3754

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dittmer D, Pati S, Zambetti G et al (1993) Gain of function mutations in p53. Nat Genet 4:42–46

    Article  CAS  PubMed  Google Scholar 

  • Ehrlich ES, Wang T, Luo K et al (2009) Regulation of Hsp90 client proteins by a Cullin5-RING E3 ubiquitin ligase. Proc Natl Acad Sci USA 106:20330–20335

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Eliyahu D, Raz A, Gruss P, Givol D, Oren M (1984) Participation of p53 cellular tumour antigen in transformation of normal embryonic cells. Nature 312:646–649

    Article  CAS  PubMed  Google Scholar 

  • Eustace BK, Jay DG (2004) Extracellular roles for the molecular chaperone, hsp90. Cell Cycle 3:1098–1100

    Article  CAS  PubMed  Google Scholar 

  • Eustace BK, Sakurai T, Stewart JK et al (2004) Functional proteomic screens reveal an essential extracellular role for hsp90 alpha in cancer cell invasiveness. Nat Cell Biol 6:507–514

    Article  CAS  PubMed  Google Scholar 

  • Freed-Pastor WA, Mizuno H, Zhao X et al (2012) Mutant p53 disrupts mammary tissue architecture via the mevalonate pathway. Cell 148:244–258

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fu S, Hou MM, Naing A et al (2015) Phase I study of pazopanib and vorinostat: a therapeutic approach for inhibiting mutant p53-mediated angiogenesis and facilitating mutant p53 degradation. Ann Oncol 26:1012–1018

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gabai VL, Mosina VA, Budagova KR, Kabakov AE (1995) Spontaneous overexpression of heat-shock proteins in Ehrlich ascites carcinoma cells during in vivo growth. Biochem Mol Biol Int 35:95–102

    CAS  PubMed  Google Scholar 

  • Gatz SA, Wiesmuller L (2006) p53 in recombination and repair. Cell Death Differ 13:1003–1016

    Article  CAS  PubMed  Google Scholar 

  • Gomez-Pastor R, Burchfiel ET, Thiele DJ (2018) Regulation of heat shock transcription factors and their roles in physiology and disease. Nat Rev Mol Cell Biol 19:4–19

    Article  CAS  PubMed  Google Scholar 

  • Haupt Y, Maya R, Kazaz A, Oren M (1997) Mdm2 promotes the rapid degradation of p53. Nature 387:296–299

    Article  CAS  PubMed  Google Scholar 

  • Hinds PW, Finlay CA, Frey AB, Levine AJ (1987) Immunological evidence for the association of p53 with a heat shock protein, hsc70, in p53-plus-ras-transformed cell lines. Mol Cell Biol 7:2863–2869

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ingallina E, Sorrentino G, Bertolio R et al (2018) Mechanical cues control mutant p53 stability through a mevalonate-RhoA axis. Nat Cell Biol 20:28–35

    Article  CAS  PubMed  Google Scholar 

  • Jackson SE (2013) Hsp90: structure and function. Top Curr Chem 328:155–240

    Article  CAS  PubMed  Google Scholar 

  • Jenkins JR, Rudge K, Currie GA (1984) Cellular immortalization by a cDNA clone encoding the transformation-associated phosphoprotein p53. Nature 312:651–654

    Article  CAS  PubMed  Google Scholar 

  • Kress M, May E, Cassingena R, May P (1979) Simian virus 40-transformed cells express new species of proteins precipitable by anti-simian virus 40 tumor serum. J Virol 31:472–483

    CAS  PubMed  PubMed Central  Google Scholar 

  • Lane DP, Crawford LV (1979) T antigen is bound to a host protein in SV40-transformed cells. Nature 278:261–263

    Article  CAS  PubMed  Google Scholar 

  • Lang GA, Iwakuma T, Suh YA et al (2004) Gain of function of a p53 hot spot mutation in a mouse model of Li-Fraumeni syndrome. Cell 119:861–872

    Article  CAS  PubMed  Google Scholar 

  • Lee MK, Teoh WW, Phang BH, Tong WM, Wang ZQ, Sabapathy K (2012) Cell-type, dose, and mutation-type specificity dictate mutant p53 functions in vivo. Cancer Cell 22:751–764

    Article  CAS  PubMed  Google Scholar 

  • Levine AJ, Momand J, Finlay CA (1991) The p53 tumour suppressor gene. Nature 351:453–456

    Article  CAS  PubMed  Google Scholar 

  • Li D, Marchenko ND (2017) ErbB2 inhibition by lapatinib promotes degradation of mutant p53 protein in cancer cells. Oncotarget 8:5823–5833

    PubMed  Google Scholar 

  • Li D, Marchenko ND, Moll UM (2011a) 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li D, Marchenko ND, Schulz R et al (2011b) Functional inactivation of endogenous MDM2 and CHIP by Hsp90 causes aberrant stabilization of mutant p53 in human cancer cells. Mol Cancer Res 9:577–588

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li D, Yallowitz A, Ozog L, Marchenko N (2014) A gain-of-function mutant p53-HSF1 feed forward circuit governs adaptation of cancer cells to proteotoxic stress. Cell Death Dis 5:e1194

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Linzer DI, Levine AJ (1979) Characterization of a 54K dalton cellular SV40 tumor antigen present in SV40-transformed cells and uninfected embryonal carcinoma cells. Cell 17:43–52

    Article  CAS  PubMed  Google Scholar 

  • Lukashchuk N, Vousden KH (2007) Ubiquitination and degradation of mutant p53. Mol Cell Biol 27:8284–8295

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mendillo ML, Santagata S, Koeva M et al (2012) HSF1 drives a transcriptional program distinct from heat shock to support highly malignant human cancers. Cell 150:549–562

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Menon V, Povirk L (2014) Involvement of p53 in the repair of DNA double strand breaks: multifaceted roles of p53 in homologous recombination repair (HRR) and non-homologous end joining (NHEJ). Subcell Biochem 85:321–336

    Article  PubMed  PubMed Central  Google Scholar 

  • Mileo AM, Fanuele M, Battaglia F et al (1990) Selective over-expression of mRNA coding for 90 KDa stress-protein in human ovarian cancer. Anticancer Res 10:903–906

    CAS  PubMed  Google Scholar 

  • Milicevic Z, Bogojevic D, Mihailovic M, Petrovic M, Krivokapic Z (2008) Molecular characterization of hsp90 isoforms in colorectal cancer cells and its association with tumour progression. Int J Oncol 32:1169–1178

    CAS  PubMed  Google Scholar 

  • Milner J, Medcalf EA, Cook AC (1991) Tumor suppressor p53: analysis of wild-type and mutant p53 complexes. Mol Cell Biol 11:12–19

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Min JN, Huang L, Zimonjic DB, Moskophidis D, Mivechi NF (2007) Selective suppression of lymphomas by functional loss of Hsf1 in a p53-deficient mouse model for spontaneous tumors. Oncogene 26:5086–5097

    Article  CAS  PubMed  Google Scholar 

  • Morton JP, Timpson P, Karim SA et al (2010) Mutant p53 drives metastasis and overcomes growth arrest/senescence in pancreatic cancer. Proc Natl Acad Sci USA 107:246–251

    Article  CAS  PubMed  Google Scholar 

  • Muller PA, Caswell PT, Doyle B et al (2009) Mutant p53 drives invasion by promoting integrin recycling. Cell 139:1327–1341

    Article  PubMed  Google Scholar 

  • Neckers L, Workman P (2012) Hsp90 molecular chaperone inhibitors: are we there yet? Clin Cancer Res 18:64–76

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Neznanov N, Komarov AP, Neznanova L, Stanhope-Baker P, Gudkov AV (2011) Proteotoxic stress targeted therapy (PSTT): induction of protein misfolding enhances the antitumor effect of the proteasome inhibitor bortezomib. Oncotarget 2:209–221

    Article  PubMed  PubMed Central  Google Scholar 

  • Nolan KD, Franco OE, Hance MW, Hayward SW, Isaacs JS (2015) Tumor-secreted Hsp90 subverts polycomb function to drive prostate tumor growth and invasion. J Biol Chem 290:8271–8282

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Olive KP, Tuveson DA, Ruhe ZC et al (2004) Mutant p53 gain of function in two mouse models of Li-Fraumeni syndrome. Cell 119:847–860

    Article  CAS  PubMed  Google Scholar 

  • Oren M, Rotter V (2010) Mutant p53 gain-of-function in cancer. Cold Spring Harb Perspect Biol 2:a001107

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Parada LF, Land H, Weinberg RA, Wolf D, Rotter V (1984) Cooperation between gene encoding p53 tumour antigen and ras in cellular transformation. Nature 312:649–651

    Article  CAS  PubMed  Google Scholar 

  • Parrales A, Ranjan A, Iyer SV et al (2016) DNAJA1 controls the fate of misfolded mutant p53 through the mevalonate pathway. Nat Cell Biol 18:1233–1243

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Peng Y, Chen L, Li C, Lu W, Chen J (2001) Inhibition of MDM2 by hsp90 contributes to mutant p53 stabilization. J Biol Chem 276:40583–40590

    Article  CAS  PubMed  Google Scholar 

  • Petitjean A, Achatz MI, Borresen-Dale AL, Hainaut P, Olivier M (2007) TP53 mutations in human cancers: functional selection and impact on cancer prognosis and outcomes. Oncogene 26:2157–2165

    Article  CAS  PubMed  Google Scholar 

  • Pratt WB (1987) Transformation of glucocorticoid and progesterone receptors to the DNA-binding state. J Cell Biochem 35:51–68

    Article  CAS  PubMed  Google Scholar 

  • Prodromou C, Roe SM, O’Brien R, Ladbury JE, Piper PW, Pearl LH (1997) Identification and structural characterization of the ATP/ADP-binding site in the Hsp90 molecular chaperone. Cell 90:65–75

    Article  CAS  PubMed  Google Scholar 

  • Roe SM, Prodromou C, O’Brien R, Ladbury JE, Piper PW, Pearl LH (1999) Structural basis for inhibition of the Hsp90 molecular chaperone by the antitumor antibiotics radicicol and geldanamycin. J Med Chem 42:260–266

    Article  CAS  PubMed  Google Scholar 

  • Saldana-Meyer R, Recillas-Targa F (2011) Transcriptional and epigenetic regulation of the p53 tumor suppressor gene. Epigenetics 6:1068–1077

    Article  CAS  PubMed  Google Scholar 

  • Sauvage F, Messaoudi S, Fattal E, Barratt G, Vergnaud-Gauduchon J (2017) Heat shock proteins and cancer: how can nanomedicine be harnessed? J Control Release 248:133–143

    Article  CAS  PubMed  Google Scholar 

  • Schulz-Heddergott R, Moll UM (2018) Gain-of-Function (GOF) mutant p53 as actionable therapeutic target. Cancers (Basel) 10:188

    Article  CAS  Google Scholar 

  • Schulz-Heddergott R, Stark N, Edmunds SJ et al (2018) Therapeutic ablation of gain-of-function mutant p53 in colorectal cancer inhibits Stat3-mediated tumor growth and invasion. Cancer Cell 34:298–314 e7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shepherd FA, Lacas B, Le Teuff G et al (2017) Pooled analysis of the prognostic and predictive effects of TP53 comutation status combined with KRAS or EGFR mutation in early-stage resected non-small-cell lung cancer in four trials of adjuvant chemotherapy. J Clin Oncol 35:2018–2027

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shyamala G, Gauthier Y, Moore SK, Catelli MG, Ullrich SJ (1989) Estrogenic regulation of murine uterine 90-kilodalton heat shock protein gene expression. Mol Cell Biol 9:3567–3570

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Soussi T (2010) The history of p53. A perfect example of the drawbacks of scientific paradigms. EMBO Rep 11:822–826

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Stuhlmiller TJ, Miller SM, Zawistowski JS et al (2015) Inhibition of Lapatinib-induced kinome reprogramming in ERBB2-positive breast cancer by targeting BET family bromodomains. Cell Rep 11:390–404

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sturzbecher HW, Addison C, Jenkins JR (1988) Characterization of mutant p53-hsp72/73 protein-protein complexes by transient expression in monkey COS cells. Mol Cell Biol 8:3740–3747

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Terzian T, Suh YA, Iwakuma T et al (2008) The inherent instability of mutant p53 is alleviated by Mdm2 or p16INK4a loss. Genes Dev 22:1337–1344

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Travers J, Sharp S, Workman P (2012) Hsp90 inhibition: two-pronged exploitation of cancer dependencies. Drug Discov Today 17:242–252

    Article  CAS  PubMed  Google Scholar 

  • Turrell FK, Kerr EM, Gao M et al (2017) Lung tumors with distinct p53 mutations respond similarly to p53 targeted therapy but exhibit genotype-specific statin sensitivity. Genes Dev 31:1339–1353

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vogelstein B, Lane D, Levine AJ (2000) Surfing the p53 network. Nature 408:307–310

    Article  CAS  PubMed  Google Scholar 

  • Weissmueller S, Manchado E, Saborowski M et al (2014) Mutant p53 drives pancreatic cancer metastasis through cell-autonomous PDGF receptor beta signaling. Cell 157:382–394

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Whitesell L, Lindquist SL (2005) Hsp90 and the chaperoning of cancer. Nat Rev Cancer 5:761–772

    Article  CAS  PubMed  Google Scholar 

  • Whitesell L, Mimnaugh EG, De Costa B, Myers CE, Neckers LM (1994) Inhibition of heat shock protein Hsp90-pp60v-src heteroprotein complex formation by benzoquinone ansamycins: essential role for stress proteins in oncogenic transformation. Proc Natl Acad Sci USA 91:8324–8328

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wijnhoven SW, Speksnijder EN, Liu X et al (2007) Dominant-negative but not gain-of-function effects of a p53.R270H mutation in mouse epithelium tissue after DNA damage. Cancer Res 67:4648–4656

    Article  CAS  PubMed  Google Scholar 

  • Willis A, Jung EJ, Wakefield T, Chen X (2004) Mutant p53 exerts a dominant negative effect by preventing wild-type p53 from binding to the promoter of its target genes. Oncogene 23:2330–2338

    Article  CAS  PubMed  Google Scholar 

  • Workman P, Burrows F, Neckers L, Rosen N (2007) Drugging the cancer chaperone Hsp90: combinatorial therapeutic exploitation of oncogene addiction and tumor stress. Ann N Y Acad Sci 1113:202–216

    Article  CAS  PubMed  Google Scholar 

  • Wu X, Bayle JH, Olson D, Levine AJ (1993) The p53-mdm-2 autoregulatory feedback loop. Genes Dev 7:1126–1132

    Article  CAS  PubMed  Google Scholar 

  • Xu W, Marcu M, Yuan X, Mimnaugh E, Patterson C, Neckers L (2002) Chaperone-dependent E3 ubiquitin ligase CHIP mediates a degradative pathway for c-ErbB2/Neu. Proc Natl Acad Sci USA 99:12847–12852

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yallowitz AR, Li D, Lobko A, Mott D, Nemajerova A, Marchenko N (2015) Mutant p53 amplifies epidermal growth factor receptor family signaling to promote mammary tumorigenesis. Mol Cancer Res 13:743–754

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yallowitz A, Ghaleb A, Garcia L, Alexandrova EM, Marchenko N (2018) Heat shock factor 1 confers resistance to lapatinib in ERBB2-positive breast cancer cells. Cell Death Dis 9:621

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Yan W, Liu G, Scoumanne A, Chen X (2008) Suppression of inhibitor of differentiation 2, a target of mutant p53, is required for gain-of-function mutations. Cancer Res 68:6789–6796

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhao Y, Liu H, Liu Z et al (2011) Overcoming trastuzumab resistance in breast cancer by targeting dysregulated glucose metabolism. Cancer Res 71:4585–4597

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

This work was supported by the Department of Defense grant W81XWH-16-1-0448 (BC151569) and the Carol Baldwin Breast Cancer Research Fund to N. Marchenko.

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Authors and Affiliations

  1. Department of Pathology, Stony Brook University, Stony Brook, NY, USA

    Amr Ghaleb & Natalia Marchenko

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  1. Amr Ghaleb
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  2. Natalia Marchenko
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Correspondence to Natalia Marchenko .

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Editors and Affiliations

  1. Department of Medicine and Director, Precision Therapeutics Proteogenomics Diagnostic Center, Eleanor N. Dana Cancer Center, University of Toledo, College of Medicine and Life Sciences, Toledo, OH, USA

    Alexzander A. A. Asea

  2. Department of Experimental Radiation Oncology, MD Anderson Cancer Center, Houston, TX, USA

    Punit Kaur

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Ghaleb, A., Marchenko, N. (2019). p53-Hsp90 Axis in Human Cancer. In: Asea, A., Kaur, P. (eds) Heat Shock Protein 90 in Human Diseases and Disorders. Heat Shock Proteins, vol 19. Springer, Cham. https://doi.org/10.1007/978-3-030-23158-3_7

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