Recent Study of Dual HDAC/PARP Inhibitor for the Treatment of Tumor

Author(s): Haiying Lu, Lan Bai, Yanping Zhou, Yongping Lu, Zhongliang Jiang*, Jianyou Shi*.

Journal Name: Current Topics in Medicinal Chemistry

Volume 19 , Issue 12 , 2019

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Graphical Abstract:


Abstract:

The occurrence and development of tumors are closely related to epigenetic instability which modulates gene expression through DNA methylation, histone modification, chromatin remodeling, and RNA-related silencing. Histone deacetylase (HDAC) and poly (ADP-ribose) polymerase (PARP) are targets of epigenetic regulation. Over the years, a large number of studies have shown that HDAC inhibitors and PARP inhibitors have synergistic effects in the treatment of tumors, and there are reports of related dual HDAC/PARP inhibitors. This review will give a brief summary of the synergistic mechanisms of HDAC inhibitors and PARP inhibitors and introduce the design of the first dual HDAC/PARP inhibitor, which may guide the design of more dual HDAC/PARP inhibitors for the treatment of tumors.

Keywords: Epigenetics, Tumor, HDAC, PARP, Dual inhibitors, Synergy.

[1]
Yoo, C.B.; Jones, P.A. Epigenetic therapy of cancer: Past, present and future. Nat. Rev. Drug Discov., 2006, 5(1), 37-50. [http://dx.doi.org/10.1038/nrd1930]. [PMID: 16485345].
[2]
Egger, G.; Liang, G.; Aparicio, A.; Jones, P.A. Epigenetics in human disease and prospects for epigenetic therapy. Nature, 2004, 429(6990), 457-463. [http://dx.doi.org/10.1038/nature02625]. [PMID: 15164071].
[3]
Mahady, L.; Nadeem, M.; Malek-Ahmadi, M.; Chen, K.; Perez, S.E.; Mufson, E.J. Frontal cortex epigenetic dysregulation during the progression of Alzheimer’s Disease. J. Alzheimers Dis., 2018, 62(1), 115-131. [http://dx.doi.org/10.3233/JAD-171032]. [PMID: 29439356].
[4]
Conway, S.J.; Woster, P.M.; Shen, J.K.; Georg, G.; Wang, S. Epigenetics: Novel therapeutics targeting epigenetics. J. Med. Chem., 2015, 58(2), 523-524. [http://dx.doi.org/10.1021/jm501941q]. [PMID: 25532017].
[5]
Falkenberg, K.J.; Johnstone, R.W. Histone deacetylases and their inhibitors in cancer, neurological diseases and immune disorders. Nat. Rev. Drug Discov., 2014, 13(9), 673-691. [http://dx.doi.org/10.1038/nrd4360]. [PMID: 25131830].
[6]
Aboeldahab, A.M.A.; Beshr, E.A.M.; Shoman, M.E.; Rabea, S.M.; Aly, O.M. Spirohydantoins and 1,2,4-triazole-3-carboxamide derivatives as inhibitors of histone deacetylase: Design, synthesis, and biological evaluation. Eur. J. Med. Chem., 2018, 146, 79-92. [http://dx.doi.org/10.1016/j.ejmech.2018.01.021]. [PMID: 29396364].
[7]
Javle, M.; Curtin, N.J. The role of PARP in DNA repair and its therapeutic exploitation. Br. J. Cancer, 2011, 105(8), 1114-1122. [http://dx.doi.org/10.1038/bjc.2011.382]. [PMID: 21989215].
[8]
Frantz, S. The trouble with making combination drugs. Nat. Rev. Drug Discov., 2006, 5(11), 881-882. [http://dx.doi.org/10.1038/nrd2188]. [PMID: 17117518].
[9]
Bilanges, B.; Torbett, N.; Vanhaesebroeck, B. Killing two kinase families with one stone. Nat. Chem. Biol., 2008, 4(11), 648-649. [http://dx.doi.org/10.1038/nchembio1108-648]. [PMID: 18936744].
[10]
Bannister, A.J.; Kouzarides, T. Regulation of chromatin by histone modifications. Cell Res., 2011, 21(3), 381-395. [http://dx.doi.org/10.1038/cr.2011.22]. [PMID: 21321607].
[11]
Icardi, L.; De Bosscher, K.; Tavernier, J. The HAT/HDAC interplay: Multilevel control of STAT signaling. Cytokine Growth Factor Rev., 2012, 23(6), 283-291. [http://dx.doi.org/10.1016/j.cytogfr.2012.08.002]. [PMID: 22989617].
[12]
West, A.C.; Johnstone, R.W. New and emerging HDAC inhibitors for cancer treatment. J. Clin. Invest., 2014, 124(1), 30-39. [http://dx.doi.org/10.1172/JCI69738]. [PMID: 24382387].
[13]
Glozak, M.A.; Sengupta, N.; Zhang, X.; Seto, E. Acetylation and deacetylation of non-histone proteins. Gene, 2005, 363, 15-23. [http://dx.doi.org/10.1016/j.gene.2005.09.010]. [PMID: 16289629].
[14]
Kekatpure, V.D.; Dannenberg, A.J.; Subbaramaiah, K. HDAC6 modulates Hsp90 chaperone activity and regulates activation of aryl hydrocarbon receptor signaling. J. Biol. Chem., 2009, 284(12), 7436-7445. [http://dx.doi.org/10.1074/jbc.M808999200]. [PMID: 19158084].
[15]
Bali, P.; Pranpat, M.; Bradner, J.; Balasis, M.; Fiskus, W.; Guo, F.; Rocha, K.; Kumaraswamy, S.; Boyapalle, S.; Atadja, P.; Seto, E.; Bhalla, K. Inhibition of histone deacetylase 6 acetylates and disrupts the chaperone function of heat shock protein 90: a novel basis for antileukemia activity of histone deacetylase inhibitors. J. Biol. Chem., 2005, 280(29), 26729-26734. [http://dx.doi.org/10.1074/jbc.C500186200]. [PMID: 15937340].
[16]
Kalin, J.H.; Bergman, J.A. Development and therapeutic implications of selective histone deacetylase 6 inhibitors. J. Med. Chem., 2013, 56(16), 6297-6313. [http://dx.doi.org/10.1021/jm4001659]. [PMID: 23627282].
[17]
Negmeldin, A.T.; Knoff, J.R.; Pflum, M.K.H. The structural requirements of histone deacetylase inhibitors: C4-modified SAHA analogs display dual HDAC6/HDAC8 selectivity. Eur. J. Med. Chem., 2018, 143, 1790-1806. [http://dx.doi.org/10.1016/j.ejmech.2017.10.076]. [PMID: 29150330].
[18]
Garnock-Jones, K.P. Panobinostat: First global approval. Drugs, 2015, 75(6), 695-704. [http://dx.doi.org/10.1007/s40265-015-0388-8]. [PMID: 25837990].
[19]
Putcha, P.; Yu, J.; Rodriguez-Barrueco, R.; Saucedo-Cuevas, L.; Villagrasa, P.; Murga-Penas, E.; Quayle, S.N.; Yang, M.; Castro, V.; Llobet-Navas, D.; Birnbaum, D.; Finetti, P.; Woodward, W.A.; Bertucci, F.; Alpaugh, M.L.; Califano, A.; Silva, J. HDAC6 activity is a non-oncogene addiction hub for inflammatory breast cancers. Breast Cancer Res., 2015, 17(1), 149. [http://dx.doi.org/10.1186/s13058-015-0658-0]. [PMID: 26643555].
[20]
Lord, C.J.; Ashworth, A. PARP inhibitors: Synthetic lethality in the clinic. Science, 2017, 355(6330), 1152-1158. [http://dx.doi.org/10.1126/science.aam7344]. [PMID: 28302823].
[21]
Yuan, Z.; Chen, S.; Chen, C.; Chen, J.; Chen, C.; Dai, Q.; Gao, C.; Jiang, Y. Design, synthesis and biological evaluation of 4-amidobenzimidazole acridine derivatives as dual PARP and Topo inhibitors for cancer therapy. Eur. J. Med. Chem., 2017, 138, 1135-1146. [http://dx.doi.org/10.1016/j.ejmech.2017.07.050]. [PMID: 28763648].
[22]
Wang, H.; Ge, W.; Jiang, W.; Li, D.; Ju, X. SRPK1 siRNA suppresses K562 cell growth and induces apoptosis via the PARP caspase3 pathway. Mol. Med. Rep., 2018, 17(1), 2070-2076. [PMID: 29138847].
[23]
Ferraris, D.V. Evolution of poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors. From concept to clinic. J. Med. Chem., 2010, 53(12), 4561-4584. [http://dx.doi.org/10.1021/jm100012m]. [PMID: 20364863].
[24]
Lord, C.J.; Tutt, A.N.; Ashworth, A. Synthetic lethality and cancer therapy: Lessons learned from the development of PARP inhibitors. Annu. Rev. Med., 2015, 66(1), 455-470. [http://dx.doi.org/10.1146/annurev-med-050913-022545]. [PMID: 25341009].
[25]
Lewin, R.; Sulkes, A.; Shochat, T.; Tsoref, D.; Rizel, S.; Liebermann, N.; Hendler, D.; Neiman, V.; Ben-Aharon, I.; Friedman, E.; Paluch-Shimon, S.; Margel, D.; Kedar, I.; Yerushalmi, R. Oncotype-DX recurrence score distribution in breast cancer patients with BRCA1/2 mutations. Breast Cancer Res. Treat., 2016, 157(3), 511-516. [http://dx.doi.org/10.1007/s10549-016-3836-6]. [PMID: 27225387].
[26]
Sharma, P.; Klemp, J.R.; Kimler, B.F.; Mahnken, J.D.; Geier, L.J.; Khan, Q.J.; Elia, M.; Connor, C.S.; McGinness, M.K.; Mammen, J.M.; Wagner, J.L.; Ward, C.; Ranallo, L.; Knight, C.J.; Stecklein, S.R.; Jensen, R.A.; Fabian, C.J.; Godwin, A.K. Germline BRCA mutation evaluation in a prospective triple-negative breast cancer registry: Implications for hereditary breast and/or ovarian cancer syndrome testing. Breast Cancer Res. Treat., 2014, 145(3), 707-714. [http://dx.doi.org/10.1007/s10549-014-2980-0]. [PMID: 24807107].
[27]
Farmer, H.; McCabe, N.; Lord, C.J.; Tutt, A.N.; Johnson, D.A.; Richardson, T.B.; Santarosa, M.; Dillon, K.J.; Hickson, I.; Knights, C.; Martin, N.M.; Jackson, S.P.; Smith, G.C.; Ashworth, A. Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature, 2005, 434(7035), 917-921. [http://dx.doi.org/10.1038/nature03445]. [PMID: 15829967].
[28]
Ha, K.; Fiskus, W.; Choi, D.S.; Bhaskara, S.; Cerchietti, L.; Devaraj, S.G.T.; Shah, B.; Sharma, S.; Chang, J.C.; Melnick, A.M.; Hiebert, S.; Bhalla, K.N. Histone deacetylase inhibitor treatment induces ‘BRCAness’ and synergistic lethality with PARP inhibitor and cisplatin against human triple negative breast cancer cells. Oncotarget, 2014, 5(14), 5637-5650. [http://dx.doi.org/10.18632/oncotarget.2154]. [PMID: 25026298].
[29]
Giannini, G.; Battistuzzi, G.; Vesci, L.; Milazzo, F.M.; De Paolis, F.; Barbarino, M.; Guglielmi, M.B.; Carollo, V.; Gallo, G.; Artali, R.; Dallavalle, S. Novel PARP-1 inhibitors based on a 2-propanoyl-3H-quinazolin-4-one scaffold. Bioorg. Med. Chem. Lett., 2014, 24(2), 462-466. [http://dx.doi.org/10.1016/j.bmcl.2013.12.048]. [PMID: 24388690].
[30]
Mirza, M.R.; Pignata, S.; Ledermann, J.A. Latest clinical evidence and further development of PARP inhibitors in ovarian cancer. Ann. Oncol., 2018, 29(6), 1366-1376. [http://dx.doi.org/10.1093/annonc/mdy174]. [PMID: 29750420].
[31]
Kristeleit, R.; Shapiro, G.I.; Burris, H.A.; Oza, A.M.; LoRusso, P.; Patel, M.R.; Domchek, S.M.; Balmaña, J.; Drew, Y.; Chen, L.M.; Safra, T.; Montes, A.; Giordano, H.; Maloney, L.; Goble, S.; Isaacson, J.; Xiao, J.; Borrow, J.; Rolfe, L.; Shapira-Frommer, R. A phase I-II study of the oral PARP inhibitor rucaparib in patients with germline BRCA1/2-mutated ovarian carcinoma or other solid tumors. Clin. Cancer Res., 2017, 23(15), 4095-4106. [http://dx.doi.org/10.1158/1078-0432.CCR-16-2796]. [PMID: 28264872].
[32]
Dréan, A.; Lord, C.J.; Ashworth, A. PARP inhibitor combination therapy. Crit. Rev. Oncol. Hematol., 2016, 108, 73-85. [http://dx.doi.org/10.1016/j.critrevonc.2016.10.010]. [PMID: 27931843].
[33]
Rasmussen, R.D.; Gajjar, M.K.; Jensen, K.E.; Hamerlik, P. Enhanced efficacy of combined HDAC and PARP targeting in glioblastoma. Mol. Oncol., 2016, 10(5), 751-763. [http://dx.doi.org/10.1016/j.molonc.2015.12.014]. [PMID: 26794465].
[34]
Chao, O.S.; Goodman, O.B. Jr Synergistic loss of prostate cancer cell viability by coinhibition of HDAC and PARP. Mol. Cancer Res., 2014, 12(12), 1755-1766. [http://dx.doi.org/10.1158/1541-7786.MCR-14-0173]. [PMID: 25127709].
[35]
Min, A.; Im, S.A.; Kim, D.K.; Song, S.H.; Kim, H.J.; Lee, K.H.; Kim, T.Y.; Han, S.W.; Oh, D.Y.; Kim, T.Y.; O’Connor, M.J.; Bang, Y.J. Histone deacetylase inhibitor, suberoylanilide hydroxamic acid (SAHA), enhances anti-tumor effects of the poly (ADP-ribose) polymerase (PARP) inhibitor olaparib in triple-negative breast cancer cells. Breast Cancer Res., 2015, 17(1), 33. [http://dx.doi.org/10.1186/s13058-015-0534-y]. [PMID: 25888415].
[36]
Jasek, E.; Gajda, M.; Lis, G.J.; Jasińska, M.; Litwin, J.A. Combinatorial effects of PARP inhibitor PJ34 and histone deacetylase inhibitor vorinostat on leukemia cell lines. Anticancer Res., 2014, 34(4), 1849-1856. [PMID: 24692719].
[37]
Baldan, F.; Mio, C.; Allegri, L.; Puppin, C.; Russo, D.; Filetti, S.; Damante, G. Synergy between HDAC and PARP inhibitors on proliferation of a human anaplastic thyroid cancer-derived cell line. Int. J. Endocrinol., 2015, 2015(4)978371 [http://dx.doi.org/10.1155/2015/978371]. [PMID: 25705225].
[38]
Ferlay, J.; Soerjomataram, I.; Dikshit, R.; Eser, S.; Mathers, C.; Rebelo, M.; Parkin, D.M.; Forman, D.; Bray, F. Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012. Int. J. Cancer, 2015, 136(5), E359-E386. [http://dx.doi.org/10.1002/ijc.29210]. [PMID: 25220842].
[39]
Dungey, F.A.; Löser, D.A.; Chalmers, A.J. Replication-dependent radiosensitization of human glioma cells by inhibition of poly(ADP-Ribose) polymerase: mechanisms and therapeutic potential. Int. J. Radiat. Oncol. Biol. Phys., 2008, 72(4), 1188-1197. [http://dx.doi.org/10.1016/j.ijrobp.2008.07.031]. [PMID: 18954712].
[40]
Kachhap, S.K.; Rosmus, N.; Collis, S.J.; Kortenhorst, M.S.; Wissing, M.D.; Hedayati, M.; Shabbeer, S.; Mendonca, J.; Deangelis, J.; Marchionni, L.; Lin, J.; Höti, N.; Nortier, J.W.; DeWeese, T.L.; Hammers, H.; Carducci, M.A. Downregulation of homologous recombination DNA repair genes by HDAC inhibition in prostate cancer is mediated through the E2F1 transcription factor. PLoS One, 2010, 5(6)e11208 [http://dx.doi.org/10.1371/journal.pone.0011208]. [PMID: 20585447].
[41]
Helleday, T.; Petermann, E.; Lundin, C.; Hodgson, B.; Sharma, R.A. DNA repair pathways as targets for cancer therapy. Nat. Rev. Cancer, 2008, 8(3), 193-204. [http://dx.doi.org/10.1038/nrc2342]. [PMID: 18256616].
[42]
Mao, Z.; Bozzella, M.; Seluanov, A.; Gorbunova, V. DNA repair by nonhomologous end joining and homologous recombination during cell cycle in human cells. Cell Cycle, 2008, 7(18), 2902-2906. [http://dx.doi.org/10.4161/cc.7.18.6679]. [PMID: 18769152].
[43]
Davis, A.J.; Chen, D.J. DNA double strand break repair via non-homologous end-joining. Transl. Cancer Res., 2013, 2(3), 130-143. [PMID: 24000320].
[44]
Duvic, M.; Vu, J. Vorinostat: A new oral histone deacetylase inhibitor approved for cutaneous T-cell lymphoma. Expert Opin. Investig. Drugs, 2007, 16(7), 1111-1120. [http://dx.doi.org/10.1517/13543784.16.7.1111]. [PMID: 17594194].
[45]
Campas-Moya, C. Romidepsin for the treatment of cutaneous T-cell lymphoma. Drugs Today (Barc), 2009, 45(11), 787-795. [http://dx.doi.org/10.1358/dot.2009.45.11.1437052]. [PMID: 20126671].
[46]
Behera, J.; Jayaprakash, V.; Sinha, B.N. Histone deacetylase inhibitors: A review on class-I specific inhibition. Mini Rev. Med. Chem., 2015, 15(9), 731-750. [http://dx.doi.org/10.2174/1389557515666150521162237]. [PMID: 25994050].
[47]
Laubach, J.P.; Moreau, P.; San-Miguel, J.F.; Richardson, P.G. Panobinostat for the treatment of multiple myeloma. Clin. Cancer Res., 2015, 21(21), 4767-4773. [http://dx.doi.org/10.1158/1078-0432.CCR-15-0530]. [PMID: 26362997].
[48]
Wobser, M.; Weber, A.; Glunz, A.; Tauch, S.; Seitz, K.; Butelmann, T.; Hesbacher, S.; Goebeler, M.; Bartz, R.; Kohlhof, H.; Schrama, D.; Houben, R. Elucidating the mechanism of action of domatinostat (4SC-202) in cutaneous T cell lymphoma cells. J. Hematol. Oncol., 2019, 12(1), 30. [http://dx.doi.org/10.1186/s13045-019-0719-4]. [PMID: 30885250].
[49]
Pili, R.; Salumbides, B.; Zhao, M.; Altiok, S.; Qian, D.; Zwiebel, J.; Carducci, M.A.; Rudek, M.A. Phase I study of the histone deacetylase inhibitor entinostat in combination with 13-cis retinoic acid in patients with solid tumours. Br. J. Cancer, 2012, 106(1), 77-84. [http://dx.doi.org/10.1038/bjc.2011.527]. [PMID: 22134508].
[50]
Younes, A.; Oki, Y.; Bociek, R.G.; Kuruvilla, J.; Fanale, M.; Neelapu, S.; Copeland, A.; Buglio, D.; Galal, A.; Besterman, J.; Li, Z.; Drouin, M.; Patterson, T.; Ward, M.R.; Paulus, J.K.; Ji, Y.; Medeiros, L.J.; Martell, R.E. Mocetinostat for relapsed classical Hodgkin’s lymphoma: An open-label, single-arm, phase 2 trial. Lancet Oncol., 2011, 12(13), 1222-1228. [http://dx.doi.org/10.1016/S1470-2045(11)70265-0]. [PMID: 22033282].
[51]
Garcia-Manero, G.; Montalban-Bravo, G.; Berdeja, J.G.; Abaza, Y.; Jabbour, E.; Essell, J.; Lyons, R.M.; Ravandi, F.; Maris, M.; Heller, B.; DeZern, A.E.; Babu, S.; Wright, D.; Anz, B.; Boccia, R.; Komrokji, R.S.; Kuriakose, P.; Reeves, J.; Sekeres, M.A.; Kantarjian, H.M.; Ghalie, R.; Roboz, G.J. Phase 2, randomized, double-blind study of pracinostat in combination with azacitidine in patients with untreated, higher-risk myelodysplastic syndromes. Cancer, 2017, 123(6), 994-1002. [http://dx.doi.org/10.1002/cncr.30533]. [PMID: 28094841].
[52]
Kim, G.; Ison, G.; McKee, A.E.; Zhang, H.; Tang, S.; Gwise, T.; Sridhara, R.; Lee, E.; Tzou, A.; Philip, R.; Chiu, H.J.; Ricks, T.K.; Palmby, T.; Russell, A.M.; Ladouceur, G.; Pfuma, E.; Li, H.; Zhao, L.; Liu, Q.; Venugopal, R.; Ibrahim, A.; Pazdur, R. FDA Approval Summary: Olaparib monotherapy in patients with deleterious germline brca-mutated advanced ovarian cancer treated with three or more lines of chemotherapy. Clin. Cancer Res., 2015, 21(19), 4257-4261. [http://dx.doi.org/10.1158/1078-0432.CCR-15-0887]. [PMID: 26187614].
[53]
Balasubramaniam, S.; Beaver, J.A.; Horton, S.; Fernandes, L.L.; Tang, S.; Horne, H.N.; Liu, J.; Liu, C.; Schrieber, S.J.; Yu, J.; Song, P.; Pierce, W.; Robertson, K.J.; Palmby, T.R.; Chiu, H.J.; Lee, E.Y.; Philip, R.; Schuck, R.; Charlab, R.; Banerjee, A.; Chen, X.H.; Wang, X.; Goldberg, K.B.; Sridhara, R.; Kim, G.; Pazdur, R. FDA approval summary: Rucaparib for the treatment of patients with deleterious BRCA mutation-associated advanced ovarian cancer. Clin. Cancer Res., 2017, 23(23), 7165-7170. [http://dx.doi.org/10.1158/1078-0432.CCR-17-1337]. [PMID: 28751443].
[54]
Ison, G.; Howie, L.J.; Amiri-Kordestani, L.; Zhang, L.; Tang, S.; Sridhara, R.; Pierre, V.; Charlab, R.; Ramamoorthy, A.; Song, P.; Li, F.; Yu, J.; Manheng, W.; Palmby, T.R.; Ghosh, S.; Horne, H.N.; Lee, E.Y.; Philip, R.; Dave, K.; Chen, X.H.; Kelly, S.L.; Janoria, K.G.; Banerjee, A.; Eradiri, O.; Dinin, J.; Goldberg, K.B.; Pierce, W.F.; Ibrahim, A.; Kluetz, P.G.; Blumenthal, G.M.; Beaver, J.A.; Pazdur, R. FDA Approval summary: Niraparib for the maintenance treatment of patients with recurrent ovarian cancer in response to platinum-based chemotherapy. Clin. Cancer Res., 2018, 24(17), 4066-4071. [http://dx.doi.org/10.1158/1078-0432.CCR-18-0042]. [PMID: 29650751].
[55]
Hoy, S.M. Talazoparib: First Global Approval. Drugs, 2018, 78(18), 1939-1946. [http://dx.doi.org/10.1007/s40265-018-1026-z]. [PMID: 30506138].
[56]
Blakeley, J.O.; Grossman, S.A.; Mikkelsen, T.; Rosenfeld, M.R.; Peereboom, D.; Nabors, L.B.; Chi, A.S.; Emmons, G.; Garcia Ribas, I.; Supko, J.G.; Desideri, S.; Ye, X. Phase I study of iniparib concurrent with monthly or continuous temozolomide dosing schedules in patients with newly diagnosed malignant gliomas. J. Neurooncol., 2015, 125(1), 123-131. [http://dx.doi.org/10.1007/s11060-015-1876-0]. [PMID: 26285766].
[57]
Loibl, S.; O’Shaughnessy, J.; Untch, M.; Sikov, W.M.; Rugo, H.S.; McKee, M.D.; Huober, J.; Golshan, M.; von Minckwitz, G.; Maag, D.; Sullivan, D.; Wolmark, N.; McIntyre, K.; Ponce Lorenzo, J.J.; Metzger Filho, O.; Rastogi, P.; Symmans, W.F.; Liu, X.; Geyer, C.E., Jr Addition of the PARP inhibitor veliparib plus carboplatin or carboplatin alone to standard neoadjuvant chemotherapy in triple-negative breast cancer (BrighTNess): a randomised, phase 3 trial. Lancet Oncol., 2018, 19(4), 497-509. [http://dx.doi.org/10.1016/S1470-2045(18)30111-6]. [PMID: 29501363].
[58]
Lee, J.H.; Choy, M.L.; Ngo, L.; Foster, S.S.; Marks, P.A. Histone deacetylase inhibitor induces DNA damage, which normal but not transformed cells can repair. Proc. Natl. Acad. Sci. USA, 2010, 107(33), 14639-14644. [http://dx.doi.org/10.1073/pnas.1008522107]. [PMID: 20679231].
[59]
Ha, K.; Fiskus, W.; Rao, R.; Balusu, R.; Venkannagari, S.; Nalabothula, N.R.; Bhalla, K.N. Hsp90 inhibitor-mediated disruption of chaperone association of ATR with hsp90 sensitizes cancer cells to DNA damage. Mol. Cancer Ther., 2011, 10(7), 1194-1206. [http://dx.doi.org/10.1158/1535-7163.MCT-11-0094]. [PMID: 21566061].
[60]
Stecklein, S.R.; Kumaraswamy, E.; Behbod, F.; Wang, W.; Chaguturu, V.; Harlan-Williams, L.M.; Jensen, R.A. BRCA1 and HSP90 cooperate in homologous and non-homologous DNA double-strand-break repair and G2/M checkpoint activation. Proc. Natl. Acad. Sci. USA, 2012, 109(34), 13650-13655. [http://dx.doi.org/10.1073/pnas.1203326109]. [PMID: 22869732].
[61]
Roos, W.P.; Krumm, A. The multifaceted influence of histone deacetylases on DNA damage signalling and DNA repair. Nucleic Acids Res., 2016, 44(21), 10017-10030. [http://dx.doi.org/10.1093/nar/gkw922]. [PMID: 27738139].
[62]
Robert, T.; Vanoli, F.; Chiolo, I.; Shubassi, G.; Bernstein, K.A.; Rothstein, R.; Botrugno, O.A.; Parazzoli, D.; Oldani, A.; Minucci, S.; Foiani, M. HDACs link the DNA damage response, processing of double-strand breaks and autophagy. Nature, 2011, 471(7336), 74-79. [http://dx.doi.org/10.1038/nature09803]. [PMID: 21368826].
[63]
Elmore, S. Apoptosis: A review of programmed cell death. Toxicol. Pathol., 2007, 35(4), 495-516. [http://dx.doi.org/10.1080/01926230701320337]. [PMID: 17562483].
[64]
Xu, W.; Yang, Z.; Zhou, S.F.; Lu, N. Posttranslational regulation of phosphatase and tensin homolog (PTEN) and its functional impact on cancer behaviors. Drug Des. Devel. Ther., 2014, 8, 1745-1751. [http://dx.doi.org/10.2147/DDDT.S71061]. [PMID: 25336918].
[65]
Baker, S.J.; McKinnon, P.J. Tumour-suppressor function in the nervous system. Nat. Rev. Cancer, 2004, 4(3), 184-196. [http://dx.doi.org/10.1038/nrc1297]. [PMID: 14993900].
[66]
Riedl, S.J.; Shi, Y. Molecular mechanisms of caspase regulation during apoptosis. Nat. Rev. Mol. Cell Biol., 2004, 5(11), 897-907. [http://dx.doi.org/10.1038/nrm1496]. [PMID: 15520809].
[67]
Siddiqui, W.A.; Ahad, A.; Ahsan, H. The mystery of BCL2 family: Bcl-2 proteins and apoptosis: an update. Arch. Toxicol., 2015, 89(3), 289-317. [http://dx.doi.org/10.1007/s00204-014-1448-7]. [PMID: 25618543].
[68]
Frank, D.O.; Dengjel, J.; Wilfling, F.; Kozjak-Pavlovic, V.; Häcker, G.; Weber, A. The pro-apoptotic BH3-only protein Bim interacts with components of the translocase of the outer mitochondrial membrane (TOM). PLoS One, 2015, 10(4)e0123341 [http://dx.doi.org/10.1371/journal.pone.0123341]. [PMID: 25875815].
[69]
Li, T.; Kon, N.; Jiang, L.; Tan, M.; Ludwig, T.; Zhao, Y.; Baer, R.; Gu, W. Tumor suppression in the absence of p53-mediated cell-cycle arrest, apoptosis, and senescence. Cell, 2012, 149(6), 1269-1283. [http://dx.doi.org/10.1016/j.cell.2012.04.026]. [PMID: 22682249].
[70]
Sivars, U.; Aivazian, D.; Pfeffer, S.R. Yip3 catalyses the dissociation of endosomal Rab-GDI complexes. Nature, 2003, 425(6960), 856-859. [http://dx.doi.org/10.1038/nature02057]. [PMID: 14574414].
[71]
Hegde, M.; Mantelingu, K.; Pandey, M.; Pavankumar, C.S.; Rangappa, K.S.; Raghavan, S.C. Combinatorial study of a novel Poly (ADP-ribose) polymerase inhibitor and an HDAC inhibitor, SAHA, in leukemic cell lines. Target. Oncol., 2016, 11(5), 655-665. [http://dx.doi.org/10.1007/s11523-016-0441-x]. [PMID: 27188390].
[72]
Kimbung, S.; Biskup, E.; Johansson, I.; Aaltonen, K.; Ottosson-Wadlund, A.; Gruvberger-Saal, S.; Cunliffe, H.; Fadeel, B.; Loman, N.; Berglund, P.; Hedenfalk, I. Co-targeting of the PI3K pathway improves the response of BRCA1 deficient breast cancer cells to PARP1 inhibition. Cancer Lett., 2012, 319(2), 232-241. [http://dx.doi.org/10.1016/j.canlet.2012.01.015]. [PMID: 22266096].
[73]
Konstantinopoulos, P.A.; Wilson, A.J.; Saskowski, J.; Wass, E.; Khabele, D. Suberoylanilide hydroxamic acid (SAHA) enhances olaparib activity by targeting homologous recombination DNA repair in ovarian cancer. Gynecol. Oncol., 2014, 133(3), 599-606. [http://dx.doi.org/10.1016/j.ygyno.2014.03.007]. [PMID: 24631446].
[74]
Paolino, D.; Cosco, D.; Gaspari, M.; Celano, M.; Wolfram, J.; Voce, P.; Puxeddu, E.; Filetti, S.; Celia, C.; Ferrari, M.; Russo, D.; Fresta, M. Targeting the thyroid gland with thyroid-stimulating hormone (TSH)-nanoliposomes. Biomaterials, 2014, 35(25), 7101-7109. [http://dx.doi.org/10.1016/j.biomaterials.2014.04.088]. [PMID: 24836306].
[75]
D’Agostino, M.; Sponziello, M.; Puppin, C.; Celano, M.; Maggisano, V.; Baldan, F.; Biffoni, M.; Bulotta, S.; Durante, C.; Filetti, S.; Damante, G.; Russo, D. Different expression of TSH receptor and NIS genes in thyroid cancer: role of epigenetics. J. Mol. Endocrinol., 2014, 52(2), 121-131. [http://dx.doi.org/10.1530/JME-13-0160]. [PMID: 24353283].
[76]
Yuan, Z.; Chen, S.; Sun, Q.; Wang, N.; Li, D.; Miao, S.; Gao, C.; Chen, Y.; Tan, C.; Jiang, Y. Olaparib hydroxamic acid derivatives as dual PARP and HDAC inhibitors for cancer therapy. Bioorg. Med. Chem., 2017, 25(15), 4100-4109. [http://dx.doi.org/10.1016/j.bmc.2017.05.058]. [PMID: 28601509].
[77]
Eskelinen, E.L. The dual role of autophagy in cancer. Curr. Opin. Pharmacol., 2011, 11(4), 294-300. [http://dx.doi.org/10.1016/j.coph.2011.03.009]. [PMID: 21498118].
[78]
Walton, E.L. The dual role of ROS, antioxidants and autophagy in cancer. Biomed. J., 2016, 39(2), 89-92. [http://dx.doi.org/10.1016/j.bj.2016.05.001]. [PMID: 27372163].
[79]
Guo, Z.R. [Strategy of molecular drug design: dual-target drug design]. Yao Xue Xue Bao, 2009, 44(3), 209-218. [PMID: 19449516].
[80]
Morphy, R.; Kay, C.; Rankovic, Z. From magic bullets to designed multiple ligands. Drug Discov. Today, 2004, 9(15), 641-651. [http://dx.doi.org/10.1016/S1359-6446(04)03163-0]. [PMID: 15279847].
[81]
Fu, R.G.S.; Sun, Y.; Sheng, W.B.; Liao, D.F. Designing multi-targeted agents: An emerging anticancer drug discovery paradigm. Eur. J. Med. Chem., 2017, 136, 195-211. [http://dx.doi.org/10.1016/j.ejmech.2017.05.016]. [PMID: 28494256].


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VOLUME: 19
ISSUE: 12
Year: 2019
Page: [1041 - 1050]
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DOI: 10.2174/1568026619666190603092407
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