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Current Cancer Drug Targets

Author(s): Han Gong, Dan Nie and Zhengyu Li*

DOI: 10.2174/1568009620999200816130218

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Targeting Six Hallmarks of Cancer in Ovarian Cancer Therapy

Page: [853 - 867] Pages: 15

  • * (Excluding Mailing and Handling)

Abstract

Normal cells must overcome multiple protective mechanisms to develop into cancer cells. Their new capabilities include self-sufficiency in growth signals and insensitivity to antigrowth signals, evasion of apoptosis, a limitless replicative potential, sustained angiogenesis, and tissue invasion and metastasis; these are also termed the six hallmarks of cancer. A deep understanding of the genetic and protein alterations involved in these processes has enabled the development of targeted therapeutic strategies and clinical trial design in the search for ovarian cancer treatments. Clinically, significantly longer progression-free survival has been observed in the single use of PARP, MEK, VEGF and Chk1/Chk2 inhibitors. However, the clinical efficacy of the targeted agents is still restricted to specific molecular subtypes and no trials illustrate a benefit in overall survival. Exploring novel drug targets or combining current feasible biological agents hold great promise to further improve outcomes in ovarian cancer. In this review, we intend to provide a comprehensive description of the molecular alterations involved in ovarian cancer carcinogenesis and of emerging biological agents and combined strategies that target aberrant pathways, which might shed light on future ovarian cancer treatment.

Keywords: Ovarian cancer, cancer hallmark, targeted therapy, PARP, MEK, VEGF.

Graphical Abstract

[1]
Bray, F.; Ferlay, J.; Soerjomataram, I.; Siegel, R.L.; Torre, L.A.; Jemal, A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin., 2018, 68(6), 394-424.
[http://dx.doi.org/10.3322/caac.21492] [PMID: 30207593]
[2]
Wiggans, A.J.; Cass, G.K.; Bryant, A.; Lawrie, T.A.; Morrison, J. Poly(ADP-ribose) polymerase (PARP) inhibitors for the treatment of ovarian cancer. Cochrane Database Syst. Rev., 2015, (5): CD007929.
[http://dx.doi.org/10.1002/14651858.CD007929.pub3] [PMID: 25991068]
[3]
Ledermann, J. A.; Raja, F. A.; Fotopoulou, C.; Gonzalez-Martin, A.; Colombo, N.; Sessa, C. Newly diagnosed and relapsed epithelial ovarian carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann. Oncol., 2018, 29(4), iv259.
[4]
Moore, K.; Colombo, N.; Scambia, G.; Kim, B.G.; Oaknin, A.; Friedlander, M.; Lisyanskaya, A.; Floquet, A.; Leary, A.; Sonke, G.S.; Gourley, C.; Banerjee, S.; Oza, A.; González-Martín, A.; Aghajanian, C.; Bradley, W.; Mathews, C.; Liu, J.; Lowe, E.S.; Bloomfield, R.; DiSilvestro, P. Maintenance olaparib in patients with newly diagnosed advanced ovarian cancer. N. Engl. J. Med., 2018, 379(26), 2495-2505.
[http://dx.doi.org/10.1056/NEJMoa1810858] [PMID: 30345884]
[5]
Hanahan, D.; Weinberg, R.A. The hallmarks of cancer. Cell, 2000, 100(1), 57-70.
[http://dx.doi.org/10.1016/S0092-8674(00)81683-9] [PMID: 10647931]
[6]
Landen, C.N., Jr; Birrer, M.J.; Sood, A.K. Early events in the pathogenesis of epithelial ovarian cancer. J. Clin. Oncol., 2008, 26(6), 995-1005.
[http://dx.doi.org/10.1200/JCO.2006.07.9970] [PMID: 18195328]
[7]
Zeineldin, R.; Muller, C.Y.; Stack, M.S.; Hudson, L.G. Targeting the EGF receptor for ovarian cancer therapy. J. Oncol., 2010, 2010, 414676.
[http://dx.doi.org/10.1155/2010/414676] [PMID: 20066160]
[8]
Bos, J.L.; Rehmann, H.; Wittinghofer, A. GEFs and GAPs: critical elements in the control of small G proteins. Cell, 2007, 129(5), 865-877.
[http://dx.doi.org/10.1016/j.cell.2007.05.018] [PMID: 17540168]
[9]
Krengel, U.; Schlichting, I.; Scherer, A.; Schumann, R.; Frech, M.; John, J.; Kabsch, W.; Pai, E.F.; Wittinghofer, A. Three-dimensional structures of H-ras p21 mutants: molecular basis for their inability to function as signal switch molecules. Cell, 1990, 62(3), 539-548.
[http://dx.doi.org/10.1016/0092-8674(90)90018-A] [PMID: 2199064]
[10]
Harrington, B.S.; Annunziata, C.M. NF-κB signaling in ovarian cancer. Cancers (Basel), 2019, 11(8), E1182.
[http://dx.doi.org/10.3390/cancers11081182] [PMID: 31443240]
[11]
Appert-Collin, A.; Hubert, P.; Crémel, G.; Bennasroune, A. Role of ErbB receptors in cancer cell migration and invasion. Front. Pharmacol., 2015, 6, 283.
[http://dx.doi.org/10.3389/fphar.2015.00283] [PMID: 26635612]
[12]
Mallmann-Gottschalk, N.; Sax, Y.; Kimmig, R.; Lang, S.; Brandau, S. EGFR-specific tyrosine kinase inhibitor modifies NK cell-mediated antitumoral activity against ovarian cancer cells. Int. J. Mol. Sci., 2019, 20(19)E4693
[http://dx.doi.org/10.3390/ijms20194693] [PMID: 31546690]
[13]
Haldar, K.; Gaitskell, K.; Bryant, A.; Nicum, S.; Kehoe, S.; Morrison, J. Epidermal growth factor receptor blockers for the treatment of ovarian cancer. Cochrane Database Syst. Rev., 2011, (10)CD007927
[http://dx.doi.org/10.1002/14651858.CD007927.pub3] [PMID: 21975775]
[14]
Zhou, X.; Shi, K.; Hao, Y.; Yang, C.; Zha, R.; Yi, C.; Qian, Z. Advances in nanotechnology-based delivery systems for EGFR tyrosine kinases inhibitors in cancer therapy. Asian J Pharm Sci, 2020, 15(1), 26-41.
[http://dx.doi.org/10.1016/j.ajps.2019.06.001] [PMID: 32175016]
[15]
Domínguez-Ríos, R.; Sánchez-Ramírez, D.R.; Ruiz-Saray, K.; Oceguera-Basurto, P.E.; Almada, M.; Juárez, J.; Zepeda-Moreno, A.; Del Toro-Arreola, A.; Topete, A.; Daneri-Navarro, A. Cisplatin-loaded PLGA nanoparticles for HER2 targeted ovarian cancer therapy. Colloids Surf. B Biointerfaces, 2019, 178, 199-207.
[http://dx.doi.org/10.1016/j.colsurfb.2019.03.011] [PMID: 30856589]
[16]
Ghassami, E.; Varshosaz, J.; Minaiyan, M.; Nasirikenari, M.; Hoseini, S.M. Biodistribution, safety and organ toxicity of docetaxel-loaded in HER-2 aptamer conjugated ecoflex® nanoparticles in a mouse xenograft model of ovarian cancer. Recent Pat. Nanotechnol., 2019, 13(1), 49-58.
[http://dx.doi.org/10.2174/1872210513666181128162403] [PMID: 30488805]
[17]
Sui, H.; Shi, C.; Yan, Z.; Li, H. Combination of erlotinib and a PARP inhibitor inhibits growth of A2780 tumor xenografts due to increased autophagy. Drug Des. Devel. Ther., 2015, 9, 3183-3190.
[http://dx.doi.org/10.2147/DDDT.S82035] [PMID: 26124641]
[18]
McCormick, F. KRAS as a Therapeutic Target. Clin. Cancer. Res., 2015, 21(8), 1797-801.
[http://dx.doi.org/10.1158/1078-0432.CCR-14-2662]
[19]
Christensen, J.G.; Olson, P.; Briere, T.; Wiel, C.; Bergo, M.O. Targeting Krasg12c -mutant cancer with a mutation-specific inhibitor. J. Intern. Med., 2020, 288(2), 183-191.
[http://dx.doi.org/10.1111/joim.13057] [PMID: 32176377]
[20]
Liu, P.; Wang, Y.; Li, X. Targeting the untargetable KRAS in cancer therapy. Acta Pharm. Sin. B, 2019, 9(5), 871-879.
[http://dx.doi.org/10.1016/j.apsb.2019.03.002] [PMID: 31649840]
[21]
Husseinzadeh, N.; Husseinzadeh, H.D. mTOR inhibitors and their clinical application in cervical, endometrial and ovarian cancers: a critical review. Gynecol. Oncol., 2014, 133(2), 375-381.
[http://dx.doi.org/10.1016/j.ygyno.2014.02.017] [PMID: 24556063]
[22]
Behbakht, K.; Sill, M.W.; Darcy, K.M.; Rubin, S.C.; Mannel, R.S.; Waggoner, S.; Schilder, R.J.; Cai, K.Q.; Godwin, A.K.; Alpaugh, R.K. Phase II trial of the mTOR inhibitor, temsirolimus and evaluation of circulating tumor cells and tumor biomarkers in persistent and recurrent epithelial ovarian and primary peritoneal malignancies: a Gynecologic Oncology Group study. Gynecol. Oncol., 2011, 123(1), 19-26.
[http://dx.doi.org/10.1016/j.ygyno.2011.06.022] [PMID: 21752435]
[23]
Della Pepa, C.; Tonini, G.; Santini, D.; Losito, S.; Pisano, C.; Di Napoli, M.; Cecere, S.C.; Gargiulo, P.; Pignata, S. Low Grade Serous Ovarian Carcinoma: from the molecular characterization to the best therapeutic strategy. Cancer Treat. Rev., 2015, 41(2), 136-143.
[http://dx.doi.org/10.1016/j.ctrv.2014.12.003] [PMID: 25573350]
[24]
Hyman, D.M.; Puzanov, I.; Subbiah, V.; Faris, J.E.; Chau, I.; Blay, J.Y.; Wolf, J.; Raje, N.S.; Diamond, E.L.; Hollebecque, A.; Gervais, R.; Elez-Fernandez, M.E.; Italiano, A.; Hofheinz, R.D.; Hidalgo, M.; Chan, E.; Schuler, M.; Lasserre, S.F.; Makrutzki, M.; Sirzen, F.; Veronese, M.L.; Tabernero, J.; Baselga, J. Vemurafenib in Multiple Nonmelanoma Cancers with BRAF V600 Mutations. N. Engl. J. Med., 2015, 373(8), 726-736.
[http://dx.doi.org/10.1056/NEJMoa1502309] [PMID: 26287849]
[25]
Farley, J.; Brady, W.E.; Vathipadiekal, V.; Lankes, H.A.; Coleman, R.; Morgan, M.A.; Mannel, R.; Yamada, S.D.; Mutch, D.; Rodgers, W.H.; Birrer, M.; Gershenson, D.M. Selumetinib in women with recurrent low-grade serous carcinoma of the ovary or peritoneum: an open-label, single-arm, phase 2 study. Lancet Oncol., 2013, 14(2), 134-140.
[http://dx.doi.org/10.1016/S1470-2045(12)70572-7] [PMID: 23261356]
[26]
Arend, R.C.; Davis, A.M.; Chimiczewski, P.; O’Malley, D.M.; Provencher, D.; Vergote, I.; Ghamande, S.; Birrer, M.J. EMR 20006-012: A phase II randomized double-blind placebo controlled trial comparing the combination of pimasertib (MEK inhibitor) with SAR245409 (PI3K inhibitor) to pimasertib alone in patients with previously treated unresectable borderline or low grade ovarian cancer. Gynecol. Oncol., 2020, 156(2), 301-307.
[http://dx.doi.org/10.1016/j.ygyno.2019.12.002] [PMID: 31870556]
[27]
Bedard, P. L.; Tabernero, J.; Janku, F.; Wainberg, Z. A.; Paz-Ares, L.; Vansteenkiste, J.; Van Cutsem, E.; Perez-Garcia, J.; Stathis, A.; Britten, C. D.; Le, N.; Carter, K.; Demanse, D.; Csonka, D.; Peters, M.; Zubel, A.; Nauwelaerts, H.; Sessa, C. A phase Ib dose-escalation study of the oral pan-PI3K inhibitor buparlisib (BKM120) in combination with the oral MEK1/2 inhibitor trametinib (GSK1120212) in patients with selected advanced solid tumors Clinical cancer research : an official journal of the American Association for Cancer Research, 2015, 21(4), 730-738.
[28]
Kinross, K.M.; Brown, D.V.; Kleinschmidt, M.; Jackson, S.; Christensen, J.; Cullinane, C.; Hicks, R.J.; Johnstone, R.W.; McArthur, G.A. In vivo activity of combined PI3K/mTOR and MEK inhibition in a Kras(G12D);Pten deletion mouse model of ovarian cancer. Mol. Cancer Ther., 2011, 10(8), 1440-1449.
[http://dx.doi.org/10.1158/1535-7163.MCT-11-0240] [PMID: 21632463]
[29]
Wainberg, Z.A.; Alsina, M.; Soares, H.P.; Braña, I.; Britten, C.D.; Del Conte, G.; Ezeh, P.; Houk, B.; Kern, K.A.; Leong, S.; Pathan, N.; Pierce, K.J.; Siu, L.L.; Vermette, J.; Tabernero, J. A multi-arm phase I study of the PI3K/mTOR inhibitors PF-04691502 and gedatolisib (PF-05212384) plus irinotecan or the MEK inhibitor PD-0325901 in advanced cancer. Target. Oncol., 2017, 12(6), 775-785.
[http://dx.doi.org/10.1007/s11523-017-0530-5] [PMID: 29067643]
[30]
Kessler, D.; Gmachl, M.; Mantoulidis, A.; Martin, L.J.; Zoephel, A.; Mayer, M.; Gollner, A.; Covini, D.; Fischer, S.; Gerstberger, T.; Gmaschitz, T.; Goodwin, C.; Greb, P.; Häring, D.; Hela, W.; Hoffmann, J.; Karolyi-Oezguer, J.; Knesl, P.; Kornigg, S.; Koegl, M.; Kousek, R.; Lamarre, L.; Moser, F.; Munico-Martinez, S.; Peinsipp, C.; Phan, J.; Rinnenthal, J.; Sai, J.; Salamon, C.; Scherbantin, Y.; Schipany, K.; Schnitzer, R.; Schrenk, A.; Sharps, B.; Siszler, G.; Sun, Q.; Waterson, A.; Wolkerstorfer, B.; Zeeb, M.; Pearson, M.; Fesik, S.W.; McConnell, D.B. Drugging an undruggable pocket on KRAS. Proc. Natl. Acad. Sci. USA, 2019, 116(32), 15823-15829.
[http://dx.doi.org/10.1073/pnas.1904529116] [PMID: 31332011]
[31]
Canon, J.; Rex, K.; Saiki, A.Y.; Mohr, C.; Cooke, K.; Bagal, D.; Gaida, K.; Holt, T.; Knutson, C.G.; Koppada, N.; Lanman, B.A.; Werner, J.; Rapaport, A.S.; San Miguel, T.; Ortiz, R.; Osgood, T.; Sun, J-R.; Zhu, X.; McCarter, J.D.; Volak, L.P.; Houk, B.E.; Fakih, M.G.; O’Neil, B.H.; Price, T.J.; Falchook, G.S.; Desai, J.; Kuo, J.; Govindan, R.; Hong, D.S.; Ouyang, W.; Henary, H.; Arvedson, T.; Cee, V.J.; Lipford, J.R. The clinical KRAS(G12C) inhibitor AMG 510 drives anti-tumour immunity. Nature, 2019, 575(7781), 217-223.
[http://dx.doi.org/10.1038/s41586-019-1694-1] [PMID: 31666701]
[32]
Nagasaka, M.; Li, Y.; Sukari, A.; Ou, S.I.; Al-Hallak, M.N.; Azmi, A.S. KRAS G12C Game of Thrones, which direct KRAS inhibitor will claim the iron throne? Cancer Treat. Rev., 2020, 84, 101974.
[http://dx.doi.org/10.1016/j.ctrv.2020.101974] [PMID: 32014824]
[33]
Kim, M. J.; Lee, S. J.; Ryu, J. H.; Kim, S. H.; Kwon, I. C.; Roberts, T. M. Combination of KRAS gene silencing and PI3K inhibition for ovarian cancer treatment J. Control. Release, 2020, 318, 98-108.
[34]
Chen, J. The cell-cycle arrest and apoptotic functions of p53 in tumor initiation and progression. Cold Spring Harb. Perspect. Med., 2016, 6(3), a026104.
[http://dx.doi.org/10.1101/cshperspect.a026104] [PMID: 26931810]
[35]
Skilling, J.S.; Sood, A.; Niemann, T.; Lager, D.J.; Buller, R.E. An abundance of p53 null mutations in ovarian carcinoma. Oncogene, 1996, 13(1), 117-123.
[PMID: 8700537]
[36]
Gurpinar, E.; Vousden, K.H. Hitting cancers’ weak spots: vulnerabilities imposed by p53 mutation. Trends Cell Biol., 2015, 25(8), 486-495.
[http://dx.doi.org/10.1016/j.tcb.2015.04.001] [PMID: 25960041]
[37]
Brown, J.S.; O’Carrigan, B.; Jackson, S.P.; Yap, T.A. Targeting DNA repair in cancer: Beyond PARP inhibitors. Cancer Discov., 2017, 7(1), 20-37.
[http://dx.doi.org/10.1158/2159-8290.CD-16-0860] [PMID: 28003236]
[38]
Guy, H.; Walder, L.; Fisher, M. Cost-effectiveness of niraparib versus routine surveillance, olaparib and rucaparib for the maintenance treatment of patients with ovarian cancer in the United States. Pharmacoeconomics, 2019, 37(3), 391-405.
[http://dx.doi.org/10.1007/s40273-018-0745-z] [PMID: 30478649]
[39]
Mirza, M.R.; Monk, B.J.; Herrstedt, J.; Oza, A.M.; Mahner, S.; Redondo, A.; Fabbro, M.; Ledermann, J.A.; Lorusso, D.; Vergote, I.; Ben-Baruch, N.E.; Marth, C.; Mądry, R.; Christensen, R.D.; Berek, J.S.; Dørum, A.; Tinker, A.V.; du Bois, A.; González-Martín, A.; Follana, P.; Benigno, B.; Rosenberg, P.; Gilbert, L.; Rimel, B.J.; Buscema, J.; Balser, J.P.; Agarwal, S.; Matulonis, U.A. ENGOT-OV16/NOVA Investigators. Niraparib maintenance therapy in platinum-sensitive, recurrent ovarian cancer. N. Engl. J. Med., 2016, 375(22), 2154-2164.
[http://dx.doi.org/10.1056/NEJMoa1611310] [PMID: 27717299]
[40]
Pujade-Lauraine, E.; Ledermann, J.A.; Selle, F.; Gebski, V.; Penson, R.T.; Oza, A.M.; Korach, J.; Huzarski, T.; Poveda, A.; Pignata, S.; Friedlander, M.; Colombo, N.; Harter, P.; Fujiwara, K.; Ray-Coquard, I.; Banerjee, S.; Liu, J.; Lowe, E.S.; Bloomfield, R.; Pautier, P. SOLO2/ENGOT-Ov21 investigators. Olaparib tablets as maintenance therapy in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT-Ov21): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol., 2017, 18(9), 1274-1284.
[http://dx.doi.org/10.1016/S1470-2045(17)30469-2] [PMID: 28754483]
[41]
Swisher, E.M.; Lin, K.K.; Oza, A.M.; Scott, C.L.; Giordano, H.; Sun, J.; Konecny, G.E.; Coleman, R.L.; Tinker, A.V.; O’Malley, D.M.; Kristeleit, R.S.; Ma, L.; Bell-McGuinn, K.M.; Brenton, J.D.; Cragun, J.M.; Oaknin, A.; Ray-Coquard, I.; Harrell, M.I.; Mann, E.; Kaufmann, S.H.; Floquet, A.; Leary, A.; Harding, T.C.; Goble, S.; Maloney, L.; Isaacson, J.; Allen, A.R.; Rolfe, L.; Yelensky, R.; Raponi, M.; McNeish, I.A. Rucaparib in relapsed, platinum-sensitive high-grade ovarian carcinoma (ARIEL2 Part 1): an international, multicentre, open-label, phase 2 trial. Lancet Oncol., 2017, 18(1), 75-87.
[http://dx.doi.org/10.1016/S1470-2045(16)30559-9] [PMID: 27908594]
[42]
Ledermann, J.; Harter, P.; Gourley, C.; Friedlander, M.; Vergote, I.; Rustin, G.; Scott, C.L.; Meier, W.; Shapira-Frommer, R.; Safra, T.; Matei, D.; Fielding, A.; Spencer, S.; Dougherty, B.; Orr, M.; Hodgson, D.; Barrett, J.C.; Matulonis, U. Olaparib maintenance therapy in patients with platinum-sensitive relapsed serous ovarian cancer: a preplanned retrospective analysis of outcomes by BRCA status in a randomised phase 2 trial. Lancet Oncol., 2014, 15(8), 852-861.
[http://dx.doi.org/10.1016/S1470-2045(14)70228-1] [PMID: 24882434]
[43]
LoRusso, P. M.; Li, J.; Burger, A.; Heilbrun, L. K.; Sausville, E. A.; Boerner, S. A.; Smith, D.; Pilat, M. J.; Zhang, J.; Tolaney, S. M.; Cleary, J. M.; Chen, A. P.; Rubinstein, L.; Boerner, J. L.; Bowditch, A.; Cai, D.; Bell, T.; Wolanski, A.; Marrero, A. M.; Zhang, Y.; Ji, J.; Ferry-Galow, K.; Kinders, R. J.; Parchment, R. E.; Shapiro, G. I.; Phase, I Phase I safety, pharmacokinetic, and pharmacodynamic study of the poly(ADP-ribose) polymerase (PARP) inhibitor veliparib (ABT-888) in combination with irinotecan in patients with advanced solid tumors Clin. Cancer. Res., 2016, 22(13), 3227-3237.
[44]
Oza, A.M.; Cibula, D.; Benzaquen, A.O.; Poole, C.; Mathijssen, R.H.J.; Sonke, G.S.; Colombo, N.; Špaček, J.; Vuylsteke, P.; Hirte, H.; Mahner, S.; Plante, M.; Schmalfeldt, B.; Mackay, H.; Rowbottom, J.; Lowe, E.S.; Dougherty, B.; Barrett, J.C.; Friedlander, M. Olaparib combined with chemotherapy for recurrent platinum-sensitive ovarian cancer: a randomised phase 2 trial. Lancet Oncol., 2015, 16(1), 87-97.
[http://dx.doi.org/10.1016/S1470-2045(14)71135-0] [PMID: 25481791]
[45]
Kummar, S.; Oza, A. M.; Fleming, G. F.; Sullivan, D. M.; Gandara, D. R.; Naughton, M. J.; Villalona-Calero, M. A.; Morgan, R. J., Jr; Szabo, P. M.; Youn, A.; Chen, A. P.; Ji, J.; Allen, D. E.; Lih, C. J.; Mehaffey, M. G.; Walsh, W. D.; McGregor, P. M., 3rd; Steinberg, S. M.; Williams, P. M.; Kinders, R. J.; Conley, B. A.; Simon, R. M.; Doroshow, J. H. Randomized Trial of Oral Cyclophosphamide and Veliparib in High-Grade Serous Ovarian, Primary Peritoneal, or Fallopian Tube Cancers, or BRCA-Mutant Ovarian Cancer. Clin. Cancer. Res., 2015, 21(7), 1574-1582.
[46]
González-Martín, A.; Pothuri, B.; Vergote, I.; DePont Christensen, R.; Graybill, W.; Mirza, M.R.; McCormick, C.; Lorusso, D.; Hoskins, P.; Freyer, G.; Baumann, K.; Jardon, K.; Redondo, A.; Moore, R.G.; Vulsteke, C.; O’Cearbhaill, R.E.; Lund, B.; Backes, F.; Barretina-Ginesta, P.; Haggerty, A.F.; Rubio-Pérez, M.J.; Shahin, M.S.; Mangili, G.; Bradley, W.H.; Bruchim, I.; Sun, K.; Malinowska, I.A.; Li, Y.; Gupta, D.; Monk, B.J. PRIMA/ENGOT-OV26/GOG-3012 Investigators. Niraparib in patients with newly diagnosed advanced ovarian cancer. N. Engl. J. Med., 2019, 381(25), 2391-2402.
[http://dx.doi.org/10.1056/NEJMoa1910962] [PMID: 31562799]
[47]
Coleman, R.L.; Fleming, G.F.; Brady, M.F.; Swisher, E.M.; Steffensen, K.D.; Friedlander, M.; Okamoto, A.; Moore, K.N.; Efrat Ben-Baruch, N.; Werner, T.L.; Cloven, N.G.; Oaknin, A.; DiSilvestro, P.A.; Morgan, M.A.; Nam, J.H.; Leath, C.A., III; Nicum, S.; Hagemann, A.R.; Littell, R.D.; Cella, D.; Baron-Hay, S.; Garcia-Donas, J.; Mizuno, M.; Bell-McGuinn, K.; Sullivan, D.M.; Bach, B.A.; Bhattacharya, S.; Ratajczak, C.K.; Ansell, P.J.; Dinh, M.H.; Aghajanian, C.; Bookman, M.A. Veliparib with first-line cChemotherapy and as maintenance therapy in ovarian cancer. N. Engl. J. Med., 2019, 381(25), 2403-2415.
[http://dx.doi.org/10.1056/NEJMoa1909707] [PMID: 31562800]
[48]
Thomas, A.; Redon, C.E.; Sciuto, L.; Padiernos, E.; Ji, J.; Lee, M-J.; Yuno, A.; Lee, S.; Zhang, Y.; Tran, L.; Yutzy, W.; Rajan, A.; Guha, U.; Chen, H.; Hassan, R.; Alewine, C.C.; Szabo, E.; Bates, S.E.; Kinders, R.J.; Steinberg, S.M.; Doroshow, J.H.; Aladjem, M.I.; Trepel, J.B.; Pommier, Y.; Phase, I. Phase I study of ATR inhibitor M6620 in combination with topotecan in patients with advanced solid tumors. J. Clin. Oncol., 2018, 36(16), 1594-1602.
[http://dx.doi.org/10.1200/JCO.2017.76.6915] [PMID: 29252124]
[49]
Bradbury, A.; Hall, S.; Curtin, N.; Drew, Y. Targeting ATR as cancer therapy: A new era for synthetic lethality and synergistic combinations? Pharmacol. Ther., 2020, 207107450
[http://dx.doi.org/10.1016/j.pharmthera.2019.107450] [PMID: 31836456]
[50]
Lee, J-M.; Nair, J.; Zimmer, A.; Lipkowitz, S.; Annunziata, C.M.; Merino, M.J.; Swisher, E.M.; Harrell, M.I.; Trepel, J.B.; Lee, M-J.; Bagheri, M.H.; Botesteanu, D-A.; Steinberg, S.M.; Minasian, L.; Ekwede, I.; Kohn, E.C. Prexasertib, a cell cycle checkpoint kinase 1 and 2 inhibitor, in BRCA wild-type recurrent high-grade serous ovarian cancer: a first-in-class proof-of-concept phase 2 study. Lancet Oncol., 2018, 19(2), 207-215.
[http://dx.doi.org/10.1016/S1470-2045(18)30009-3] [PMID: 29361470]
[51]
Ivy, S.P.; Kunos, C.A.; Arnaldez, F.I.; Kohn, E.C. Defining and targeting wild-type BRCA high-grade serous ovarian cancer: DNA repair and cell cycle checkpoints. Expert Opin. Investig. Drugs, 2019, 28(9), 771-785.
[http://dx.doi.org/10.1080/13543784.2019.1657403] [PMID: 31449760]
[52]
Reinhardt, H.C.; Aslanian, A.S.; Lees, J.A.; Yaffe, M.B. p53-deficient cells rely on ATM- and ATR-mediated checkpoint signaling through the p38MAPK/MK2 pathway for survival after DNA damage. Cancer Cell, 2007, 11(2), 175-189.
[http://dx.doi.org/10.1016/j.ccr.2006.11.024] [PMID: 17292828]
[53]
Reinhardt, H.C.; Hasskamp, P.; Schmedding, I.; Morandell, S.; van Vugt, M.A.; Wang, X.; Linding, R.; Ong, S.E.; Weaver, D.; Carr, S.A.; Yaffe, M.B. DNA damage activates a spatially distinct late cytoplasmic cell-cycle checkpoint network controlled by MK2-mediated RNA stabilization. Mol. Cell, 2010, 40(1), 34-49.
[http://dx.doi.org/10.1016/j.molcel.2010.09.018] [PMID: 20932473]
[54]
Morandell, S.; Reinhardt, H.C.; Cannell, I.G.; Kim, J.S.; Ruf, D.M.; Mitra, T.; Couvillon, A.D.; Jacks, T.; Yaffe, M.B. A reversible gene-targeting strategy identifies synthetic lethal interactions between MK2 and p53 in the DNA damage response in vivo. Cell Rep., 2013, 5(4), 868-877.
[http://dx.doi.org/10.1016/j.celrep.2013.10.025] [PMID: 24239348]
[55]
Phoa, A.F.; Recasens, A.; Gurgis, F.M.S.; Betts, T.A.; Menezes, S.V.; Chau, D.; Nordfors, K.; Haapasalo, J.; Haapasalo, H.; Johns, T.G.; Stringer, B.W.; Day, B.W.; Buckland, M.E.; Lalaoui, N.; Munoz, L. MK2 inhibition induces p53-dependent senescence in glioblastoma cells. Cancers (Basel), 2020, 12(3)E654
[http://dx.doi.org/10.3390/cancers12030654] [PMID: 32168910]
[56]
Hombach, A.; Köhler, H.; Rappl, G.; Abken, H. Human CD4+ T cells lyse target cells via granzyme/perforin upon circumvention of MHC class II restriction by an antibody-like immunoreceptor. J. Immunol., 2006, 177(8), 5668-5675.
[http://dx.doi.org/10.4049/jimmunol.177.8.5668] [PMID: 17015756]
[57]
Jindal, V.; Arora, E.; Gupta, S.; Lal, A.; Masab, M.; Potdar, R. Prospects of chimeric antigen receptor T cell therapy in ovarian cancer. Med. Oncol., 2018, 35(5), 70.
[http://dx.doi.org/10.1007/s12032-018-1131-6] [PMID: 29651744]
[58]
Tanyi, J. L.; Haas, A. R.; Beatty, G. L.; Stashwick, C. J.; O'Hara, M. H.; Morgan, M. A.; Porter, D. L.; Melenhorst, J. J.; Plesa, G.; Lacey, S. F.; June, C. H. Anti-mesothelin chimeric antigen receptor T cells in patients with epithelial ovarian cancer Journal of Clinical Oncology, 2016, 34(15), 5511-5511.
[http://dx.doi.org/10.1200/JCO.2016.34.15_suppl.5511]
[59]
González-Martín, A.; Sánchez-Lorenzo, L. Immunotherapy with checkpoint inhibitors in patients with ovarian cancer: Still promising? Cancer, 2019, 125(Suppl. 24), 4616-4622.
[http://dx.doi.org/10.1002/cncr.32520] [PMID: 31967676]
[60]
Lee, E.K.; Konstantinopoulos, P.A. Combined PARP and immune checkpoint inhibition in ovarian cancer. Trends Cancer, 2019, 5(9), 524-528.
[http://dx.doi.org/10.1016/j.trecan.2019.06.004] [PMID: 31474356]
[61]
Ding, L.; Kim, H.J.; Wang, Q.; Kearns, M.; Jiang, T.; Ohlson, C.E.; Li, B.B.; Xie, S.; Liu, J.F.; Stover, E.H.; Howitt, B.E.; Bronson, R.T.; Lazo, S.; Roberts, T.M.; Freeman, G.J.; Konstantinopoulos, P.A.; Matulonis, U.A.; Zhao, J.J. PARP inhibition elicits STING-dependent antitumor immunity in brca1-deficient ovarian cancer. Cell Rep., 2018, 25(11), 2972-2980.e5.
[http://dx.doi.org/10.1016/j.celrep.2018.11.054] [PMID: 30540933]
[62]
Konstantinopoulos, P.A.; Waggoner, S.; Vidal, G.A.; Mita, M.; Moroney, J.W.; Holloway, R.; Van Le, L.; Sachdev, J.C.; Chapman-Davis, E.; Colon-Otero, G.; Penson, R.T.; Matulonis, U.A.; Kim, Y.B.; Moore, K.N.; Swisher, E.M.; Färkkilä, A.; D’Andrea, A.; Stringer-Reasor, E.; Wang, J.; Buerstatte, N.; Arora, S.; Graham, J.R.; Bobilev, D.; Dezube, B.J.; Munster, P. Single-arm phases 1 and 2 trial of niraparib in combination with pembrolizumab in patients with recurrent platinum-resistant ovarian carcinoma. JAMA Oncol., 2019.
[http://dx.doi.org/10.1001/jamaoncol.2019.1048] [PMID: 31194228]
[63]
Spring, L.M.; Wander, S.A.; Andre, F.; Moy, B.; Turner, N.C.; Bardia, A. Cyclin-dependent kinase 4 and 6 inhibitors for hormone receptor-positive breast cancer: past, present, and future. Lancet, 2020, 395(10226), 817-827.
[http://dx.doi.org/10.1016/S0140-6736(20)30165-3] [PMID: 32145796]
[64]
Konecny, G.E. Combining PARP and CDK4/6 inhibitors in MYC driven ovarian cancer. EBioMedicine, 2019, 43, 9-10.
[http://dx.doi.org/10.1016/j.ebiom.2019.04.009] [PMID: 30979685]
[65]
Maoz, A.; Ciccone, M.A.; Matsuzaki, S.; Coleman, R.L.; Matsuo, K. Emerging serine-threonine kinase inhibitors for treating ovarian cancer. Expert Opin. Emerg. Drugs, 2019, 24(4), 239-253.
[http://dx.doi.org/10.1080/14728214.2019.1696773] [PMID: 31755325]
[66]
Do, K.; Wilsker, D.; Ji, J.; Zlott, J.; Freshwater, T.; Kinders, R.J.; Collins, J.; Chen, A.P.; Doroshow, J.H.; Kummar, S.; Phase, I. Phase I study of single-agent AZD1775 (MK-1775), a wee1 kinase inhibitor, in patients with refractory solid tumors. J. Clin. Oncol., 2015, 33(30), 3409-3415.
[http://dx.doi.org/10.1200/JCO.2014.60.4009] [PMID: 25964244]
[67]
Luo, Y.; Yi, Y.; Yao, Z. Growth arrest in ovarian cancer cells by hTERT inhibition short-hairpin RNA targeting human telomerase reverse transcriptase induces immediate growth inhibition but not necessarily induces apoptosis in ovarian cancer cells. Cancer Invest., 2009, 27(10), 960-970.
[http://dx.doi.org/10.3109/07357900802491451] [PMID: 19909010]
[68]
Xie, X.; Hsu, J.L.; Choi, M-G.; Xia, W.; Yamaguchi, H.; Chen, C-T.; Trinh, B.Q.; Lu, Z.; Ueno, N.T.; Wolf, J.K.; Bast, R.C., Jr; Hung, M-C. A novel hTERT promoter-driven E1A therapeutic for ovarian cancer. Mol. Cancer Ther., 2009, 8(8), 2375-2382.
[http://dx.doi.org/10.1158/1535-7163.MCT-09-0056] [PMID: 19671744]
[69]
Takakura, M.; Nakamura, M.; Kyo, S.; Hashimoto, M.; Mori, N.; Ikoma, T.; Mizumoto, Y.; Fujiwara, T.; Urata, Y.; Inoue, M. Intraperitoneal administration of telomerase-specific oncolytic adenovirus sensitizes ovarian cancer cells to cisplatin and affects survival in a xenograft model with peritoneal dissemination. Cancer Gene Ther., 2010, 17(1), 11-19.
[http://dx.doi.org/10.1038/cgt.2009.44] [PMID: 19662088]
[70]
Burger, R.A.; Brady, M.F.; Bookman, M.A.; Fleming, G.F.; Monk, B.J.; Huang, H.; Mannel, R.S.; Homesley, H.D.; Fowler, J.; Greer, B.E.; Boente, M.; Birrer, M.J.; Liang, S.X. Gynecologic Oncology Group. Incorporation of bevacizumab in the primary treatment of ovarian cancer. N. Engl. J. Med., 2011, 365(26), 2473-2483.
[http://dx.doi.org/10.1056/NEJMoa1104390] [PMID: 22204724]
[71]
Perren, T.J.; Swart, A.M.; Pfisterer, J.; Ledermann, J.A.; Pujade-Lauraine, E.; Kristensen, G.; Carey, M.S.; Beale, P.; Cervantes, A.; Kurzeder, C.; du Bois, A.; Sehouli, J.; Kimmig, R.; Stähle, A.; Collinson, F.; Essapen, S.; Gourley, C.; Lortholary, A.; Selle, F.; Mirza, M.R.; Leminen, A.; Plante, M.; Stark, D.; Qian, W.; Parmar, M.K.B.; Oza, A.M. ICON7 Investigators. A phase 3 trial of bevacizumab in ovarian cancer. N. Engl. J. Med., 2011, 365(26), 2484-2496.
[http://dx.doi.org/10.1056/NEJMoa1103799] [PMID: 22204725]
[72]
Aghajanian, C.; Blank, S.V.; Goff, B.A.; Judson, P.L.; Teneriello, M.G.; Husain, A.; Sovak, M.A.; Yi, J.; Nycum, L.R. OCEANS: a randomized, double-blind, placebo-controlled phase III trial of chemotherapy with or without bevacizumab in patients with platinum-sensitive recurrent epithelial ovarian, primary peritoneal, or fallopian tube cancer. J. Clin. Oncol., 2012, 30(17), 2039-2045.
[http://dx.doi.org/10.1200/JCO.2012.42.0505] [PMID: 22529265]
[73]
Pujade-Lauraine, E.; Hilpert, F.; Weber, B.; Reuss, A.; Poveda, A.; Kristensen, G.; Sorio, R.; Vergote, I.; Witteveen, P.; Bamias, A.; Pereira, D.; Wimberger, P.; Oaknin, A.; Mirza, M.R.; Follana, P.; Bollag, D.; Ray-Coquard, I. Bevacizumab combined with chemotherapy for platinum-resistant recurrent ovarian cancer: The AURELIA open-label randomized phase III trial. J. Clin. Oncol., 2014, 32(13), 1302-1308.
[http://dx.doi.org/10.1200/JCO.2013.51.4489] [PMID: 24637997]
[74]
du Bois, A.; Floquet, A.; Kim, J.W.; Rau, J.; del Campo, J.M.; Friedlander, M.; Pignata, S.; Fujiwara, K.; Vergote, I.; Colombo, N.; Mirza, M.R.; Monk, B.J.; Kimmig, R.; Ray-Coquard, I.; Zang, R.; Diaz-Padilla, I.; Baumann, K.H.; Mouret-Reynier, M.A.; Kim, J.H.; Kurzeder, C.; Lesoin, A.; Vasey, P.; Marth, C.; Canzler, U.; Scambia, G.; Shimada, M.; Calvert, P.; Pujade-Lauraine, E.; Kim, B.G.; Herzog, T.J.; Mitrica, I.; Schade-Brittinger, C.; Wang, Q.; Crescenzo, R.; Harter, P. Incorporation of pazopanib in maintenance therapy of ovarian cancer. J. Clin. Oncol., 2014, 32(30), 3374-3382.
[http://dx.doi.org/10.1200/JCO.2014.55.7348] [PMID: 25225436]
[75]
du Bois, A.; Kristensen, G.; Ray-Coquard, I.; Reuss, A.; Pignata, S.; Colombo, N.; Denison, U.; Vergote, I.; Del Campo, J.M.; Ottevanger, P.; Heubner, M.; Minarik, T.; Sevin, E.; de Gregorio, N.; Bidziński, M.; Pfisterer, J.; Malander, S.; Hilpert, F.; Mirza, M.R.; Scambia, G.; Meier, W.; Nicoletto, M.O.; Bjørge, L.; Lortholary, A.; Sailer, M.O.; Merger, M.; Harter, P. AGO Study Group led Gynecologic Cancer Intergroup/European Network of Gynaecologic Oncology Trials Groups Intergroup Consortium. Standard first-line chemotherapy with or without nintedanib for advanced ovarian cancer (AGO-OVAR 12): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet Oncol., 2016, 17(1), 78-89.
[http://dx.doi.org/10.1016/S1470-2045(15)00366-6] [PMID: 26590673]
[76]
Ledermann, J.A.; Hackshaw, A.; Kaye, S.; Jayson, G.; Gabra, H.; McNeish, I.; Earl, H.; Perren, T.; Gore, M.; Persic, M.; Adams, M.; James, L.; Temple, G.; Merger, M.; Rustin, G. Randomized phase II placebo-controlled trial of maintenance therapy using the oral triple angiokinase inhibitor BIBF 1120 after chemotherapy for relapsed ovarian cancer. J. Clin. Oncol., 2011, 29(28), 3798-3804.
[http://dx.doi.org/10.1200/JCO.2010.33.5208] [PMID: 21859991]
[77]
Ledermann, J.A.; Embleton, A.C.; Raja, F.; Perren, T.J.; Jayson, G.C.; Rustin, G.J.S.; Kaye, S.B.; Hirte, H.; Eisenhauer, E.; Vaughan, M.; Friedlander, M.; González-Martín, A.; Stark, D.; Clark, E.; Farrelly, L.; Swart, A.M.; Cook, A.; Kaplan, R.S.; Parmar, M.K.B. ICON6 collaborators. Cediranib in patients with relapsed platinum-sensitive ovarian cancer (ICON6): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet, 2016, 387(10023), 1066-1074.
[http://dx.doi.org/10.1016/S0140-6736(15)01167-8] [PMID: 27025186]
[78]
Pignata, S.; Lorusso, D.; Scambia, G.; Sambataro, D.; Tamberi, S.; Cinieri, S.; Mosconi, A.M.; Orditura, M.; Brandes, A.A.; Arcangeli, V.; Panici, P.B.; Pisano, C.; Cecere, S.C.; Di Napoli, M.; Raspagliesi, F.; Maltese, G.; Salutari, V.; Ricci, C.; Daniele, G.; Piccirillo, M.C.; Di Maio, M.; Gallo, C.; Perrone, F. MITO 11 investigators. Pazopanib plus weekly paclitaxel versus weekly paclitaxel alone for platinum-resistant or platinum-refractory advanced ovarian cancer (MITO 11): a randomised, open-label, phase 2 trial. Lancet Oncol., 2015, 16(5), 561-568.
[http://dx.doi.org/10.1016/S1470-2045(15)70115-4] [PMID: 25882986]
[79]
Herzog, T.J.; Scambia, G.; Kim, B.G.; Lhommé, C.; Markowska, J.; Ray-Coquard, I.; Sehouli, J.; Colombo, N.; Shan, M.; Petrenciuc, O.; Oza, A. A randomized phase II trial of maintenance therapy with Sorafenib in front-line ovarian carcinoma. Gynecol. Oncol., 2013, 130(1), 25-30.
[http://dx.doi.org/10.1016/j.ygyno.2013.04.011] [PMID: 23591401]
[80]
Monk, B.J.; Poveda, A.; Vergote, I.; Raspagliesi, F.; Fujiwara, K.; Bae, D.S.; Oaknin, A.; Ray-Coquard, I.; Provencher, D.M.; Karlan, B.Y.; Lhommé, C.; Richardson, G.; Rincón, D.G.; Coleman, R.L.; Herzog, T.J.; Marth, C.; Brize, A.; Fabbro, M.; Redondo, A.; Bamias, A.; Tassoudji, M.; Navale, L.; Warner, D.J.; Oza, A.M. Anti-angiopoietin therapy with trebananib for recurrent ovarian cancer (TRINOVA-1): a randomised, multicentre, double-blind, placebo-controlled phase 3 trial. Lancet Oncol., 2014, 15(8), 799-808.
[http://dx.doi.org/10.1016/S1470-2045(14)70244-X] [PMID: 24950985]
[81]
Karlan, B.Y.; Oza, A.M.; Richardson, G.E.; Provencher, D.M.; Hansen, V.L.; Buck, M.; Chambers, S.K.; Ghatage, P.; Pippitt, C.H., Jr; Brown, J.V., III; Covens, A.; Nagarkar, R.V.; Davy, M.; Leath, C.A., III; Nguyen, H.; Stepan, D.E.; Weinreich, D.M.; Tassoudji, M.; Sun, Y.N.; Vergote, I.B. Randomized, double-blind, placebo-controlled phase II study of AMG 386 combined with weekly paclitaxel in patients with recurrent ovarian cancer. J. Clin. Oncol., 2012, 30(4), 362-371.
[http://dx.doi.org/10.1200/JCO.2010.34.3178] [PMID: 22184370]
[82]
Li, X.; Zhu, S.; Hong, C.; Cai, H. Angiogenesis inhibitors for patients with ovarian cancer: a meta-analysis of 12 randomized controlled trials. Curr. Med. Res. Opin., 2016, 32(3), 555-562.
[http://dx.doi.org/10.1185/03007995.2015.1131152] [PMID: 26652645]
[83]
Liu, M.C.; Tewari, K.S. Anti-angiogenesis therapy, synthetic lethality, and checkpoint inhibition in ovarian cancer: state of the science and novel combinations. Drugs Context, 2018, 7212558
[http://dx.doi.org/10.7573/dic.212558] [PMID: 30627206]
[84]
Ray-Coquard, I.; Pautier, P.; Pignata, S.; Pérol, D.; González-Martín, A.; Berger, R.; Fujiwara, K.; Vergote, I.; Colombo, N.; Mäenpää, J.; Selle, F.; Sehouli, J.; Lorusso, D.; Guerra Alía, E.M.; Reinthaller, A.; Nagao, S.; Lefeuvre-Plesse, C.; Canzler, U.; Scambia, G.; Lortholary, A.; Marmé, F.; Combe, P.; de Gregorio, N.; Rodrigues, M.; Buderath, P.; Dubot, C.; Burges, A.; You, B.; Pujade-Lauraine, E.; Harter, P. PAOLA-1 Investigators. Olaparib plus bevacizumab as first-line maintenance in ovarian cancer. N. Engl. J. Med., 2019, 381(25), 2416-2428.
[http://dx.doi.org/10.1056/NEJMoa1911361] [PMID: 31851799]
[85]
Gale, N.W.; Holland, S.J.; Valenzuela, D.M.; Flenniken, A.; Pan, L.; Ryan, T.E.; Henkemeyer, M.; Strebhardt, K.; Hirai, H.; Wilkinson, D.G.; Pawson, T.; Davis, S.; Yancopoulos, G.D. Eph receptors and ligands comprise two major specificity subclasses and are reciprocally compartmentalized during embryogenesis. Neuron, 1996, 17(1), 9-19.
[http://dx.doi.org/10.1016/S0896-6273(00)80276-7] [PMID: 8755474]
[86]
Landen, C.N., Jr; Lu, C.; Han, L.Y.; Coffman, K.T.; Bruckheimer, E.; Halder, J.; Mangala, L.S.; Merritt, W.M.; Lin, Y.G.; Gao, C.; Schmandt, R.; Kamat, A.A.; Li, Y.; Thaker, P.; Gershenson, D.M.; Parikh, N.U.; Gallick, G.E.; Kinch, M.S.; Sood, A.K. Efficacy and antivascular effects of EphA2 reduction with an agonistic antibody in ovarian cancer. J. Natl. Cancer Inst., 2006, 98(21), 1558-1570.
[http://dx.doi.org/10.1093/jnci/djj414] [PMID: 17077358]
[87]
Landen, C.N.; Kinch, M.S.; Sood, A.K. EphA2 as a target for ovarian cancer therapy. Expert Opin. Ther. Targets, 2005, 9(6), 1179-1187.
[http://dx.doi.org/10.1517/14728222.9.6.1179] [PMID: 16300469]
[88]
Levanon, K.; Crum, C.; Drapkin, R. New insights into the pathogenesis of serous ovarian cancer and its clinical impact. J. Clin. Oncol., 2008, 26(32), 5284-5293.
[http://dx.doi.org/10.1200/JCO.2008.18.1107] [PMID: 18854563]
[89]
Kobayashi, M.; Sawada, K.; Kimura, T. Potential of integrin inhibitors for treating ovarian cancer: A literature review. Cancers (Basel), 2017, 9(7), E83.
[http://dx.doi.org/10.3390/cancers9070083] [PMID: 28698469]
[90]
Sawada, K.; Mitra, A.K.; Radjabi, A.R.; Bhaskar, V.; Kistner, E.O.; Tretiakova, M.; Jagadeeswaran, S.; Montag, A.; Becker, A.; Kenny, H.A.; Peter, M.E.; Ramakrishnan, V.; Yamada, S.D.; Lengyel, E. Loss of E-cadherin promotes ovarian cancer metastasis via alpha 5-integrin, which is a therapeutic target. Cancer Res., 2008, 68(7), 2329-2339.
[http://dx.doi.org/10.1158/0008-5472.CAN-07-5167] [PMID: 18381440]
[91]
Bell-McGuinn, K.M.; Matthews, C.M.; Ho, S.N.; Barve, M.; Gilbert, L.; Penson, R.T.; Lengyel, E.; Palaparthy, R.; Gilder, K.; Vassos, A.; McAuliffe, W.; Weymer, S.; Barton, J.; Schilder, R.J. A phase II, single-arm study of the anti-α5β1 integrin antibody volociximab as monotherapy in patients with platinum-resistant advanced epithelial ovarian or primary peritoneal cancer. Gynecol. Oncol., 2011, 121(2), 273-279.
[http://dx.doi.org/10.1016/j.ygyno.2010.12.362] [PMID: 21276608]
[92]
Stone, R.L.; Baggerly, K.A.; Armaiz-Pena, G.N.; Kang, Y.; Sanguino, A.M.; Thanapprapasr, D.; Dalton, H.J.; Bottsford-Miller, J.; Zand, B.; Akbani, R.; Diao, L.; Nick, A.M.; DeGeest, K.; Lopez-Berestein, G.; Coleman, R.L.; Lutgendorf, S.; Sood, A.K. Focal adhesion kinase: an alternative focus for anti-angiogenesis therapy in ovarian cancer. Cancer Biol. Ther., 2014, 15(7), 919-929.
[http://dx.doi.org/10.4161/cbt.28882] [PMID: 24755674]
[93]
Golubovskaya, V.M.; Nyberg, C.; Zheng, M.; Kweh, F.; Magis, A.; Ostrov, D.; Cance, W.G. A small molecule inhibitor, 1,2,4,5-benzenetetraamine tetrahydrochloride, targeting the y397 site of focal adhesion kinase decreases tumor growth. J. Med. Chem., 2008, 51(23), 7405-7416.
[http://dx.doi.org/10.1021/jm800483v] [PMID: 18989950]
[94]
Halder, J.; Lin, Y.G.; Merritt, W.M.; Spannuth, W.A.; Nick, A.M.; Honda, T.; Kamat, A.A.; Han, L.Y.; Kim, T.J.; Lu, C.; Tari, A.M.; Bornmann, W.; Fernandez, A.; Lopez-Berestein, G.; Sood, A.K. Therapeutic efficacy of a novel focal adhesion kinase inhibitor TAE226 in ovarian carcinoma. Cancer Res., 2007, 67(22), 10976-10983.
[http://dx.doi.org/10.1158/0008-5472.CAN-07-2667] [PMID: 18006843]
[95]
Shahzad, M.M.; Lu, C.; Lee, J.W.; Stone, R.L.; Mitra, R.; Mangala, L.S.; Lu, Y.; Baggerly, K.A.; Danes, C.G.; Nick, A.M.; Halder, J.; Kim, H.S.; Vivas-Mejia, P.; Landen, C.N.; Lopez-Berestein, G.; Coleman, R.L.; Sood, A.K. Dual targeting of EphA2 and FAK in ovarian carcinoma. Cancer Biol. Ther., 2009, 8(11), 1027-1034.
[http://dx.doi.org/10.4161/cbt.8.11.8523] [PMID: 19395869]