Molecular Targeting of RRM2, NF-κB, and Mutant TP53 for the Treatment of Triple-Negative Breast Cancer.

Szczegóły
Abstrakt

Tytuł:: Molecular Targeting of RRM2, NF-κB, and Mutant TP53 for the Treatment of Triple-Negative Breast Cancer.
Autorzy:: Wilson EA; Department of Physiology and Pharmacology, Thomas J. Long School of Pharmacy, University of the Pacific, Stockton, California.
Sultana N; Department of Physiology and Pharmacology, Thomas J. Long School of Pharmacy, University of the Pacific, Stockton, California.
Shah KN; Department of Physiology and Pharmacology, Thomas J. Long School of Pharmacy, University of the Pacific, Stockton, California.
Elford HL; Molecules for Health, Inc., Richmond, Virginia.
Faridi JS; Department of Physiology and Pharmacology, Thomas J. Long School of Pharmacy, University of the Pacific, Stockton, California. .
Źródło:: Molecular cancer therapeutics [Mol Cancer Ther] 2021 Apr; Vol. 20 (4), pp. 655-664. Date of Electronic Publication: 2021 Feb 03.
Typ publikacji:: Journal Article; Research Support, Non-U.S. Gov't
Język:: English
Imprint Name(s):: Original Publication: Philadelphia, PA : American Association for Cancer Research, Inc., c2001-
MeSH Terms:: Molecular Targeted Therapy/*methods
NF-kappa B/*metabolism
Ribonucleoside Diphosphate Reductase/*metabolism
Triple Negative Breast Neoplasms/*genetics
Tumor Suppressor Protein p53/*metabolism
Animals ; Apoptosis ; Cell Proliferation ; Female ; Humans ; Mice ; Mice, Nude ; Signal Transduction ; Triple Negative Breast Neoplasms/pathology
References:: Jhan JR, Andrechek ER. Triple-negative breast cancer and the potential for targeted therapy. Pharmacogenomics. 2017;18:1595–609.
Schmid P, Rugo HS, Adams S, Schneeweiss A, Barrios CH, Iwata H, et al. Atezolizumab plus nab-paclitaxel as first-line treatment for unresectable, locally advanced or metastatic triple-negative breast cancer (IMpassion130): updated efficacy results from a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2020;21:44–59.
Robson ME, Tung N, Conte P, Im S-A, Senkus E, Xu B, et al. OlympiAD final overall survival and tolerability results: Olaparib versus chemotherapy treatment of physician's choice in patients with a germline BRCA mutation and HER2-negative metastatic breast cancer. Ann Oncol. 2019;30:558–66.
Nakhjavani M, Hardingham JE, Palethorpe HM, Price TJ, Townsend AR. Druggable molecular targets for the treatment of triple negative breast cancer. J Breast Cancer. 2019;22:341–61.
García-Aranda M, Redondo M. Immunotherapy: a challenge of breast cancer treatment. Cancers. 2019;11:1822.
Mehanna J, Haddad FGH, Eid R, Lambertini M, Kourie HR. Triple-negative breast cancer: current perspective on the evolving therapeutic landscape. Int J Womens Health. 2019;11:431–7.
Duxbury MS, Whang EE. RRM2 induces NF-kappaB-dependent MMP-9 activation and enhances cellular invasiveness. Biochem Biophys Res Commun. 2007;354:190–6.
Zhang H, Liu X, Warden CD, Huang Y, Loera S, Xue L, et al. Prognostic and therapeutic significance of ribonucleotide reductase small subunit M2 in estrogen-negative breast cancers. BMC Cancer. 2014;14:664.
Veale D, Carmichael J, Cantwell Bm, Elford Hl, Blackie R, Kerr Dj, et al. A phase 1 and pharmacokinetic study of didox: a ribonucleotide reductase inhibitor. Br J Cancer. 1988;58:70–2.
Aly A, Shah R, Hill K, Botteman MF. Overall survival, costs and healthcare resource use by number of regimens received in elderly patients with newly diagnosed metastatic triple-negative breast cancer. Future Oncol. 2019;15:1007–20.
Elford HL, Freese M, Passamani E, Morris HP. Ribonucleotide reductase and cell proliferation. I. Variations of ribonucleotide reductase activity with tumor growth rate in a series of rat hepatomas. J Biol Chem. 1970;245:5228–33.
Tanaka H, Arakawa H, Yamaguchi T, Shiraishi K, Fukuda S, Matsui K, et al. A ribonucleotide reductase gene involved in a p53-dependent cell-cycle checkpoint for DNA damage. Nature. 2000;404:42–9.
Zhou B-S, Tsai P, Ker R, Tsai J, Ho R, Yu J, et al. Overexpression of transfected human ribonucleotide reductase M2 subunit in human cancer cells enhances their invasive potential. Clin Exp Metastasis. 1998;16:43–9.
Shah KN, Mehta KR, Peterson D, Evangelista M, Livesey JC, Faridi JS. AKT-induced tamoxifen resistance is overturned by RRM2 inhibition. Mol Cancer Res. 2014;12:394–407.
Shah KN, Wilson EA, Malla R, Elford HL, Faridi JS. Targeting ribonucleotide reductase M2 and NF-kappaB activation with didox to circumvent tamoxifen resistance in breast cancer. Mol Cancer Ther. 2015;14:2411–21.
Putluri N, Maity S, Kommagani R, Creighton CJ, Putluri V, Chen F, et al. Pathway-centric integrative analysis identifies RRM2 as a prognostic marker in breast cancer associated with poor survival and tamoxifen resistance. Neoplasia. 2014;16:390–402.
Koleck TA, Conley YP. Identification and prioritization of candidate genes for symptom variability in breast cancer survivors based on disease characteristics at the cellular level. Breast Cancer. 2016;8:29–37.
Li J-P, Zhang X-M, Zhang Z, Zheng Li-H, Jindal S, Liu Y-J. Association of p53 expression with poor prognosis in patients with triple-negative breast invasive ductal carcinoma. Medicine. 2019;98:e15449.
Gong MT, Ye SD, Lv WW, He K, Li WX. Comprehensive integrated analysis of gene expression datasets identifies key anti-cancer targets in different stages of breast cancer. Exp Ther Med. 2018;16:802–10.
Chen W-X, Yang L-G, Xu L-Y, Cheng L, Qian Qi, Sun Li, et al. Bioinformatics analysis revealing prognostic significance of RRM2 gene in breast cancer. Biosci Rep. 2019;39:BSR20182062.
Lane DP. Cancer. p53, guardian of the genome. Nature. 1992;358:15–6.
Harris SL, Levine AJ. The p53 pathway: positive and negative feedback loops. Oncogene. 2005;24:2899–908.
Silwal-Pandit L, Langerød A, Børresen-Dale AL. TP53 mutations in breast and ovarian cancer. Cold Spring Harb Perspect Med. 2017;7:a026252.
Qamar S, Khokhar M, Farooq S, Ashraf S, Humayon W, Rehman A. Association of p53 overexpression with hormone receptor status and triple negative breast carcinoma. J Coll Physicians Surg Pak. 2019;29:164–7.
Elford HL, Wampler GL, van't Riet B. New ribonucleotide reductase inhibitors with antineoplastic activity. Cancer Res. 1979;39:844–51.
Elford HL, Van't Riet B, Wampler GL, Lin AL, Elford RM. Regulation of ribonucleotide reductase in mammalian cells by chemotherapeutic agents. Adv Enzyme Regul. 1980;19:151–68.
Khaleel SA, Al-Abd AM, Ali AA, Abdel-Naim AB. Didox and resveratrol sensitize colorectal cancer cells to doxorubicin via activating apoptosis and ameliorating P-glycoprotein activity. Sci Rep. 2016;6:36855.
Carmichael J, Cantwell B, Mannix KA, Veale D, Elford HL, Blackie R, et al. A phase I and pharmacokinetic study of didox administered by 36 hour infusion. The cancer research campaign phase I/II clinical trials committee. Br J Cancer. 1990;61:447–50.
Chou TC. Theoretical basis, experimental design, and computerized simulation of synergism and antagonism in drug combination studies. Pharmacol Rev. 2006;58:621–81.
Ossovskaya V, Wang Y, Budoff A, Xu Q, Lituev A, Potapova O, et al. Exploring molecular pathways of triple-negative breast cancer. Genes Cancer. 2011;2:870–9.
Dalmases A, González I, Menendez S, Arpí O, Corominas JM, Servitja S, et al. Deficiency in p53 is required for doxorubicin induced transcriptional activation of NF-кB target genes in human breast cancer. Oncotarget. 2014;5:196–210.
Kim J-Y, Jung HH, Ahn S, Bae S, Lee SEK, Kim SW, et al. The relationship between nuclear factor (NF)-κB family gene expression and prognosis in triple-negative breast cancer (TNBC) patients receiving adjuvant doxorubicin treatment. Sci Rep. 2016;6:31804.
Turner N, Moretti E, Siclari O, Migliaccio I, Santarpia L, D'Incalci M, et al. Targeting triple negative breast cancer: is p53 the answer?. Cancer Treat Rev. 2013;39:541–50.
Yadav BS, Chanana P, Jhamb S. Biomarkers in triple negative breast cancer: a review. World J Clin Oncol. 2015;6:252–63.
Horigome E, Fujieda M, Handa T, Katayama A, Ito M, Ichihara A, et al. Mutant TP53 modulates metastasis of triple negative breast cancer through adenosine A2b receptor signaling. Oncotarget. 2018;9:34554–66.
Duffy MJ, Synnott NC, Crown J. Mutant p53 in breast cancer: potential as a therapeutic target and biomarker. Breast Cancer Res Treat. 2018;170:213–9.
Nik-Zainal S, Davies H, Staaf J, Ramakrishna M, Glodzik D, Zou X, et al. Landscape of somatic mutations in 560 breast cancer whole-genome sequences. Nature. 2016;534:47–54.
Bae SY, Nam SJ, Jung Y, Lee SB, Park B-W, Lim W, et al. Differences in prognosis and efficacy of chemotherapy by p53 expression in triple-negative breast cancer. Breast Cancer Res Treat. 2018;172:437–44.
Hashmi AA, Naz S, Hashmi SK, Hussain ZF, Irfan M, Khan EY, et al. Prognostic significance of p16 & p53 immunohistochemical expression in triple negative breast cancer. BMC Clin Pathol. 2018;18:9.
Kollareddy M, Dimitrova E, Vallabhaneni KC, Chan A, Le T, Chauhan KM, et al. Regulation of nucleotide metabolism by mutant p53 contributes to its gain-of-function activities. Nat Commun. 2015;6:7389.
Rubens RD, Kaye SB, Soukop M, Williams CJ, Brampton MH, Harris AL. Phase II trial of didox in advanced breast cancer. Cancer research campaign phase I/II clinical trials committee. Br J Cancer. 1991;64:1187–8.
Al-Abd AM, Al-Abbasi FA, Asaad GF, Abdel-Naim AB. Didox potentiates the cytotoxic profile of doxorubicin and protects from its cardiotoxicity. Eur J Pharmacol. 2013;718:361–9.
Licata S, Saponiero A, Mordente A, Minotti G. Doxorubicin metabolism and toxicity in human myocardium: role of cytoplasmic deglycosidation and carbonyl reduction. Chem Res Toxicol. 2000;13:414–20.
Elford HL, Cardounel AJ, Zweier J, Henry J, Sumpter R, Oakley O, et al. Didox, a unique ribonucleotide reductase inhibitor and free radical scavenger, can protect against doxorubicin caused cardiotoxicity with enhanced antitumor activity. Cancer Res. 2006;66:502.
Substance Nomenclature:: 0 (NF-kappa B)
0 (Tumor Suppressor Protein p53)
EC 1.17.4.- (ribonucleotide reductase M2)
EC 1.17.4.1 (Ribonucleoside Diphosphate Reductase)
Entry Date(s):: Date Created: 20210204 Date Completed: 20211119 Latest Revision: 20211119
Update Code:: 20240105
DOI:: 10.1158/1535-7163.MCT-20-0373
PMID:: 33536192
: Czasopismo naukowe

Doxorubicin and other anthracycline derivatives are frequently used as part of the adjuvant chemotherapy regimen for triple-negative breast cancer (TNBC). Although effective, doxorubicin is known for its off-target and toxic side effect profile, particularly with respect to the myocardium, often resulting in left ventricular (LV) dysfunction and congestive heart failure when used at cumulative doses exceeding 400 mg/m 2 Previously, we have observed that the ribonucleotide reductase subunit M2 (RRM2) is significantly overexpressed in estrogen receptor (ER)-negative cells as compared with ER-positive breast cancer cells. Here, we inhibited RRM2 in ER-negative breast cancer cells as a target for therapy in this difficult-to-treat population. We observed that through the use of didox, a ribonucleotide reductase inhibitor, the reduction in RRM2 was accompanied by reduced NF-κB activity in vitro When didox was used in combination with doxorubicin, we observed significant downregulation of NF-κB proteins accompanied by reduced TNBC cell proliferation. As well, we observed that protein levels of mutant p53 were significantly reduced by didox or combination therapy in vitro Xenograft studies showed that combination therapy was found to be synergistic in vivo , resulting in a significantly reduced tumor volume as compared with doxorubicin monotherapy. In addition, the use of didox was also found to ameliorate the toxic myocardial effects of doxorubicin in vivo as measured by heart mass, LV diameter, and serum troponin T levels. The data present a novel and promising approach for the treatment of TNBC that merits further clinical evaluation in humans.
(©2021 American Association for Cancer Research.)

Informacja