Recent Progress and Development of Small Molecule Kinase Inhibitors for the Treatment of Breast Cancer

Page: [4 - 19] Pages: 16

  • * (Excluding Mailing and Handling)

Abstract

Breast cancer, the most common health burden to women globally, is considered a major cause of death for women every year. Many signal transduction pathways can cause breast cancer. The kinase inhibitors can interrupt the signaling pathways, minimize tumor growth and consequently cure the disease. The scientists have discovered many kinase inhibitors as targeted drugs for breast cancer. In recent years, the inhibitors of EGFR, HER2, VEGFR, PI3K, CDK4/6, PARP and hormone receptor have been studied well for curing breast cancer. The FDA has approved a few kinase drugs such as trastuzumab, lapatinib, neratinib, palbociclib, abemaciclib, alpelisib to treat breast cancer recently. In this review, we summarized the latest development of kinase inhibitors as breast cancer therapy.

Keywords: Breast cancer, CDK4/6, HER2, inhibitor, kinase, PI3K, signal transduction.

Graphical Abstract

[1]
DeSantis, C.E.; Ma, J.; Gaudet, M.M.; Newman, L.A.; Miller, K.D.; Goding Sauer, A.; Jemal, A.; Siegel, R.L. Breast cancer statistics, 2019. CA Cancer J. Clin., 2019, 69(6), 438-451.
[PMID: 31577379]
[2]
Dai, X.; Li, T.; Bai, Z.; Yang, Y.; Liu, X.; Zhan, J.; Shi, B. Breast cancer intrinsic subtype classification, clinical use and future trends. Am. J. Cancer Res., 2015, 5(10), 2929-2943.
[PMID: 26693050]
[3]
Dawood, S. Triple-negative breast cancer: epidemiology and management options. Drugs, 2010, 70(17), 2247-2258.
[PMID: 21080741]
[4]
Tamimi, R.M.; Colditz, G.A.; Hazra, A.; Baer, H.J.; Hankinson, S.E.; Rosner, B.; Marotti, J.; Connolly, J.L.; Schnitt, S.J.; Collins, L.C. Traditional breast cancer risk factors in relation to molecular subtypes of breast cancer. Breast Cancer Res. Treat., 2012, 131(1), 159-167.
[PMID: 21830014]
[5]
Lin, N.U.; Winer, E.P. Brain metastases: the HER2 paradigm. Clin. Cancer Res., 2007, 13(6), 1648-1655.
[PMID: 17363517]
[6]
Martin, A.M.; Cagney, D.N.; Catalano, P.J.; Warren, L.E.; Bellon, J.R.; Punglia, R.S.; Claus, E.B.; Lee, E.Q.; Wen, P.Y.; Haas-Kogan, D.A.; Alexander, B.M.; Lin, N.U.; Aizer, A.A. Brain metastases in newly diagnosed breast cancer: a population-based study. JAMA Oncol., 2017, 3(8), 1069-1077.
[PMID: 28301662]
[7]
Hanahan, D.; Weinberg, R.A. Hallmarks of cancer: the next generation. Cell, 2011, 144(5), 646-674.
[PMID: 21376230]
[8]
Marino, M.; Galluzzo, P.; Ascenzi, P. Estrogen signaling multiple pathways to impact gene transcription. Curr. Genomics, 2006, 7(8), 497-508.
[PMID: 18369406]
[9]
Lin, N.U.; Winer, E.P. New targets for therapy in breast cancer: small molecule tyrosine kinase inhibitors. Breast Cancer Res., 2004, 6(5), 204-210.
[PMID: 15318926]
[10]
Ménard, S.; Fortis, S.; Castiglioni, F.; Agresti, R.; Balsari, A. HER2 as a prognostic factor in breast cancer. Oncology, 2001, 61(Suppl. 2), 67-72.
[PMID: 11694790]
[11]
Vivanco, I.; Sawyers, C.L. The phosphatidylinositol 3-Kinase AKT pathway in human cancer. Nat. Rev. Cancer, 2002, 2(7), 489-501.
[PMID: 12094235]
[12]
Cantley, L.C. The phosphoinositide 3-kinase pathway. Science, 2002, 296(5573), 1655-1657.
[PMID: 12040186]
[13]
Hennessy, B.T.; Smith, D.L.; Ram, P.T.; Lu, Y.; Mills, G.B. Exploiting the PI3K/AKT pathway for cancer drug discovery. Nat. Rev. Drug Discov., 2005, 4(12), 988-1004.
[PMID: 16341064]
[14]
Tamura, M.; Gu, J.; Matsumoto, K.; Aota, S.; Parsons, R.; Yamada, K.M. Inhibition of cell migration, spreading, and focal adhesions by tumor suppressor PTEN. Science, 1998, 280(5369), 1614-1617.
[PMID: 9616126]
[15]
Parsons, S.J.; Parsons, J.T. Src family kinases, key regulators of signal transduction. Oncogene, 2004, 23(48), 7906-7909.
[PMID: 15489908]
[16]
Elsberger, B. Translational evidence on the role of Src kinase and activated Src kinase in invasive breast cancer. Crit. Rev. Oncol. Hematol., 2014, 89(3), 343-351.
[PMID: 24388104]
[17]
Burotto, M.; Chiou, V.L.; Lee, J-M.; Kohn, E.C. The MAPK pathway across different malignancies: a new perspective. Cancer, 2014, 120(22), 3446-3456.
[PMID: 24948110]
[18]
Dhillon, A.S.; Hagan, S.; Rath, O.; Kolch, W. MAP kinase signalling pathways in cancer. Oncogene, 2007, 26(22), 3279-3290.
[PMID: 17496922]
[19]
Qi, X.; Yin, N.; Ma, S.; Lepp, A.; Tang, J.; Jing, W.; Johnson, B.; Dwinell, M.B.; Chitambar, C.R.; Chen, G. p38γ MAPK is a therapeutic target for triple-negative breast cancer by stimulation of cancer stem-like cell expansion. Stem Cells, 2015, 33(9), 2738-2747.
[PMID: 26077647]
[20]
Huang, S.; Wang, D.; Zhang, S.; Huang, X.; Wang, D.; Ijaz, M.; Shi, Y. Tunicamycin potentiates paclitaxel-induced apoptosis through inhibition of PI3K/AKT and MAPK pathways in breast cancer. Cancer Chemother. Pharmacol., 2017, 80(4), 685-696.
[PMID: 28779263]
[21]
Johnson, J.; Thijssen, B.; McDermott, U.; Garnett, M.; Wessels, L.F.A.; Bernards, R. Targeting the RB-E2F pathway in breast cancer. Oncogene, 2016, 35(37), 4829-4835.
[PMID: 26923330]
[22]
Sakkiah, S.; Cao, G.P.; Gupta, S.P.; Lee, K.W. Overview of the structure and function of protein kinases. Curr. Enzym. Inhib., 2017, 13.
[23]
Singh, J.C.; Jhaveri, K.; Esteva, F.J. HER2-positive advanced breast cancer: optimizing patient outcomes and opportunities for drug development. Br. J. Cancer, 2014, 111(10), 1888-1898.
[PMID: 25025958]
[24]
Nielsen, D.L.; Kümler, I.; Palshof, J.A.E.; Andersson, M. Efficacy of HER2-targeted therapy in metastatic breast cancer. Monoclonal antibodies and tyrosine kinase inhibitors. Breast, 2013, 22(1), 1-12.
[PMID: 23084121]
[25]
Nahta, R.; Hung, M-C.; Esteva, F.J. The HER-2-targeting antibodies trastuzumab and pertuzumab synergistically inhibit the survival of breast cancer cells. Cancer Res., 2004, 64(7), 2343-2346.
[PMID: 15059883]
[26]
Weil, R.J.; Palmieri, D.C.; Bronder, J.L.; Stark, A.M.; Steeg, P.S. Breast cancer metastasis to the central nervous system. Am. J. Pathol., 2005, 167(4), 913-920.
[PMID: 16192626]
[27]
Swain, S.M.; Baselga, J.; Kim, S-B.; Ro, J.; Semiglazov, V.; Campone, M.; Ciruelos, E.; Ferrero, J-M.; Schneeweiss, A.; Heeson, S.; Clark, E.; Ross, G.; Benyunes, M.C.; Cortés, J. Pertuzumab, trastuzumab, and docetaxel in HER2-positive metastatic breast cancer. N. Engl. J. Med., 2015, 372(8), 724-734.
[PMID: 25693012]
[28]
FDA Grants Regular Approval to Pertuzumab for Adjuvant Treatment of HER2-Positive Breast Cancer.
[29]
Nelson, M.H.; Dolder, C.R. A review of lapatinib ditosylate in the treatment of refractory or advanced breast cancer. Ther. Clin. Risk Manag., 2007, 3(4), 665-673.
[PMID: 18472989]
[30]
Higa, G.M.; Abraham, J. Lapatinib in the treatment of breast cancer. Expert Rev. Anticancer Ther., 2007, 7(9), 1183-1192.
[PMID: 17892419]
[31]
Cameron, D.; Casey, M.; Press, M.; Lindquist, D.; Pienkowski, T.; Romieu, C.G.; Chan, S.; Jagiello-Gruszfeld, A.; Kaufman, B.; Crown, J.; Chan, A.; Campone, M.; Viens, P.; Davidson, N.; Gorbounova, V.; Raats, J.I.; Skarlos, D.; Newstat, B.; Roychowdhury, D.; Paoletti, P.; Oliva, C.; Rubin, S.; Stein, S.; Geyer, C.E. A phase III randomized comparison of lapatinib plus capecitabine versus capecitabine alone in women with advanced breast cancer that has progressed on trastuzumab: updated efficacy and biomarker analyses. Breast Cancer Res. Treat., 2008, 112(3), 533-543.
[PMID: 18188694]
[32]
Awada, A.; Colomer, R.; Inoue, K.; Bondarenko, I.; Badwe, R.A.; Demetriou, G.; Lee, S-C.; Mehta, A.O.; Kim, S-B.; Bachelot, T.; Goswami, C.; Deo, S.; Bose, R.; Wong, A.; Xu, F.; Yao, B.; Bryce, R.; Carey, L.A. Neratinib plus paclitaxel vs. trastuzumab plus paclitaxel in previously untreated metastatic ERBB2-positive breast cancer: the NEfERT-T randomized clinical trial. JAMA Oncol., 2016, 2(12), 1557-1564.
[PMID: 27078022]
[33]
Chan, A.; Delaloge, S.; Holmes, F.A.; Moy, B.; Iwata, H.; Harvey, V.J.; Robert, N.J.; Silovski, T.; Gokmen, E.; von Minckwitz, G.; Ejlertsen, B.; Chia, S.K.L.; Mansi, J.; Barrios, C.H.; Gnant, M.; Buyse, M.; Gore, I.; Smith, J., II; Harker, G.; Masuda, N.; Petrakova, K.; Zotano, A.G.; Iannotti, N.; Rodriguez, G.; Tassone, P.; Wong, A.; Bryce, R.; Ye, Y.; Yao, B.; Martin, M. Neratinib after trastuzumab-based adjuvant therapy in patients with HER2-positive breast cancer (ExteNET): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol., 2016, 17(3), 367-377.
[PMID: 26874901]
[34]
Martin, M.; Holmes, F.A.; Ejlertsen, B.; Delaloge, S.; Moy, B.; Iwata, H.; von Minckwitz, G.; Chia, S.K.L.; Mansi, J.; Barrios, C.H.; Gnant, M.; Tomašević, Z.; Denduluri, N.; Šeparović, R.; Gokmen, E.; Bashford, A.; Ruiz Borrego, M.; Kim, S-B.; Jakobsen, E.H.; Ciceniene, A.; Inoue, K.; Overkamp, F.; Heijns, J.B.; Armstrong, A.C.; Link, J.S.; Joy, A.A.; Bryce, R.; Wong, A.; Moran, S.; Yao, B.; Xu, F.; Auerbach, A.; Buyse, M.; Chan, A.; Harvey, V.; Tomek, R.; Robert, N.J.; Gore, I.; Smith, J.W.; Masuda, N.; Di Sean Kendall, S.; Harker, W.G.; Petrakova, K.; Guerrero Zotano, A.; Simon, A.R.; Konstantinovic, Z.N.; Iannotti, N.O.; Tassone, P.; Rodriguez, G.I.; Jáñez Martinez, N.; Crespo Massieu, C.; Smickoska, S.; Somali, I.; Yilmaz, U.; Alonso, M.G.; Rosales, A.M.; Cold, S.; Knoop, A.S.; Patt, D.; Hellerstedt, B.A.; Morales Murillo, S.; Mayer, I.A.; Means-Powell, J.A.; Hui, R.; Senecal, F.M.; De Boer, R.H.; Shen, Z.; Luczak, A.A.; Chui, J.W.Y.; Tsang, J.W.; Lang, I.; Rai, Y.; Hozumi, Y.; Ten Tije, A.J.; Bhandari, M.; Osborne, C.R.C.; Ohtani, S.; Higaki, K.; Watanabe, K.; Taguchi, K.; Takahashi, M.; Filipovic, S.; Hansen, V.L.; Rao, V.P.; Gupta, M.; Petrov, P.; Coudert, B.; Vojnovic, Z.; Polya, Z.; Miyaki, T.; Yamamoto, N.; Brincat, S.; Lesniewski-Kmak, K.; Chmielowska, E.; Birhiray, R.E.; Citron, M.L.; Papish, S.W.; Berry, W.R.; Langkjer, S.T.; Garcia Sáenz, J.A.; Arance, A.M.; Efrat, N.; Sarosiek, T.; Grzeda, L.; Manalo, Y.; Smith, J.C.; Vaziri, I.; Healey, T.; Rahim, Y.; Luk, C.; Dingle, B.; Franco, S.; Sorensen, P.G.; Anand, A.; Khan, S.; Fountzilas, G.; Aogi, K.; Shimizu, S.; Mikulova, M.; Spanik, S.; Somer, R.A.; Flynn, P.J.; Coward, J.; Mainwaring, P.; Jerusalem, G.; Segura-Ojezzar, C.; Levy, C.; Delozier, T.; Khayat, D.; Coleman, R.E.; Rolles, M.J.; Maisano, R.; Nardi, M.; Ito, Y.; Yumuk, P.F.; Basaran, G.; Serdar Turhal, N.; Wilkinson, M.J.; Green, N.B.; Sidrys, A.P.; Hallmeyer, S.; Testori, D.J.; Sridhar, S.; Chang, J.; Sun, Q.; Jara-Sanchez, C.; Rubio, X.; Garrido, M.L.; De La Haba Rodriguez, J.R.; Perello Martorell, A.; Avelia Mestre, A.; Rifa Ferrer, J.; del Barco Berron, S.; Nagy, Z.; Tanaka, M. Neratinib after trastuzumab-based adjuvant therapy in HER2-positive breast cancer (ExteNET): 5-year analysis of a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol., 2017, 18(12), 1688-1700.
[PMID: 29146401]
[35]
Saura, C.; Oliveira, M.; Feng, Y-H.; Dai, M-S.; Hurvitz, S.A.; Kim, S-B.; Moy, B.; Delaloge, S.; Gradishar, W.J.; Masuda, N.; Palacova, M.; Trudeau, M.E.; Mattson, J.; Yap, Y.S.; Bryce, R.; Yao, B.; Bebchuk, J.D.; Keyvanjah, K.; Brufsky, A. NALA Investigators. Neratinib + Capecitabine versus Lapatinib + Capecitabine in Patients with HER2+ Metastatic Breast Cancer Previously Treated with ≥ 2 HER2-Directed Regimens: Findings from the Multinational, Randomized, Phase III NALA Trial. J. Clin. Oncol., 2019, 37, 1002-1002.
[36]
Li, X.; Yang, C.; Wan, H.; Zhang, G.; Feng, J.; Zhang, L.; Chen, X.; Zhong, D.; Lou, L.; Tao, W.; Zhang, L. Discovery and development of pyrotinib: A novel irreversible EGFR/HER2 dual tyrosine kinase inhibitor with favorable safety profiles for the treatment of breast cancer. Eur. J. Pharm. Sci., 2017, 110, 51-61.
[PMID: 28115222]
[37]
Xu, B.; Ma, F.; Chen, S.; Li, Q.; Yang, F.; Zhang, Y.; Chen, X.; Zhong, D.; Zhang, G. A phase I study for tolerability, safety, and pharmacokinetics of pyrotinib, a novel irreversible HER2 and EGFR inhibitor, in chinese patients with HER2+ metastatic breast cancer. J. Clin. Oncol., 2015, 33, e11596-e11596.
[38]
Li, D.; Ambrogio, L.; Shimamura, T.; Kubo, S.; Takahashi, M.; Chirieac, L.R.; Padera, R.F.; Shapiro, G.I.; Baum, A.; Himmelsbach, F.; Rettig, W.J.; Meyerson, M.; Solca, F.; Greulich, H.; Wong, K-K. BIBW2992, an irreversible EGFR/HER2 inhibitor highly effective in preclinical lung cancer models. Oncogene, 2008, 27(34), 4702-4711.
[PMID: 18408761]
[39]
Minkovsky, N.; Berezov, A. BIBW-2992, a dual receptor tyrosine kinase inhibitor for the treatment of solid tumors. Curr. Opin. Investig. Drugs, 2008, 9(12), 1336-1346.
[PMID: 19037840]
[40]
Cortés, J.; Dieras, V.; Ro, J.; Barriere, J.; Bachelot, T.; Hurvitz, S.; Le Rhun, E.; Espié, M.; Kim, S-B.; Schneeweiss, A.; Sohn, J.H.; Nabholtz, J-M.; Kellokumpu-Lehtinen, P-L.; Taguchi, J.; Piacentini, F.; Ciruelos, E.; Bono, P.; Ould-Kaci, M.; Roux, F.; Joensuu, H. Afatinib alone or afatinib plus vinorelbine versus investigator’s choice of treatment for HER2-positive breast cancer with progressive brain metastases after trastuzumab, lapatinib, or both (LUX-Breast 3): a randomised, open-label, multicentre, phase 2 trial. Lancet Oncol., 2015, 16(16), 1700-1710.
[PMID: 26596672]
[41]
Moulder, S.L.; Borges, V.F.; Baetz, T.; Mcspadden, T.; Fernetich, G.; Murthy, R.K.; Chavira, R.; Guthrie, K.; Barrett, E.; Chia, S.K. Phase, I. Phase I Study of ONT-380, a HER2 inhibitor, in patients with HER2+-advanced solid tumors, with an expansion cohort in HER2+ Metastatic Breast Cancer (MBC). Clin. Cancer Res., 2017, 23(14), 3529-3536.
[PMID: 28053022]
[42]
Duchnowska, R.; Loibl, S.; Jassem, J. Tyrosine kinase inhibitors for brain metastases in HER2-positive breast cancer. Cancer Treat. Rev., 2018, 67, 71-77.
[PMID: 29772459]
[43]
Hamilton, E.; Murthy, R.; Ferrario, C.; Conlin, A.; Krop, I.; Falkson, C.; Khan, Q.; Chamberlain, M.; Gray, T.; Borges, V. Abstract , pp. 5-20.Proceedings of the Poster Session Abstracts, 2018 , 5-
[44]
Murthy, R.; Borges, V.F.; Conlin, A.; Chaves, J.; Chamberlain, M.; Gray, T.; Vo, A.; Hamilton, E. Tucatinib with capecitabine and trastuzumab in advanced HER2-positive metastatic breast cancer with and without brain metastases: a non-randomised, open-label, phase 1b study. Lancet Oncol., 2018, 19(7), 880-888.
[PMID: 29804905]
[45]
Das, D.; Hong, J. Irreversible kinase inhibitors targeting to cysteine residues and their applications in cancer therapy. Mini Rev. Med. Chem., 2020, 20, XXXX.
[46]
Das, D.; Hong, J. Recent advancements of 4-aminoquinazoline derivatives as kinase inhibitors and their applications in medicinal chemistry. Eur. J. Med. Chem., 2019, 170, 55-72.
[PMID: 30878832]
[47]
Das, D.; Xie, L.; Wang, J.; Xu, X.; Zhang, Z.; Shi, J.; Le, X.; Hong, J. Discovery of new quinazoline derivatives as irreversible dual EGFR/HER2 inhibitors and their anticancer activities - Part 1. Bioorg. Med. Chem. Lett., 2019, 29(4), 591-596.
[PMID: 30600209]
[49]
Das, D.; Sikdar, P.; Bairagi, M. Recent developments of 2-aminothiazoles in medicinal chemistry. Eur. J. Med. Chem., 2016, 109, 89-98.
[PMID: 26771245]
[50]
Lombardo, L.J.; Lee, F.Y.; Chen, P.; Norris, D.; Barrish, J.C.; Behnia, K.; Castaneda, S.; Cornelius, L.A.M.; Das, J.; Doweyko, A.M.; Fairchild, C.; Hunt, J.T.; Inigo, I.; Johnston, K.; Kamath, A.; Kan, D.; Klei, H.; Marathe, P.; Pang, S.; Peterson, R.; Pitt, S.; Schieven, G.L.; Schmidt, R.J.; Tokarski, J.; Wen, M-L.; Wityak, J.; Borzilleri, R.M. Discovery of N-(2-chloro-6-methyl- phenyl)-2-(6-(4-(2-hydroxyethyl)- piperazin-1-yl)-2-methylpyrimidin-4- ylamino)thiazole-5-carboxamide (BMS-354825), a dual Src/Abl kinase inhibitor with potent antitumor activity in preclinical assays. J. Med. Chem., 2004, 47(27), 6658-6661.
[PMID: 15615512]
[51]
Das, J.; Chen, P.; Norris, D.; Padmanabha, R.; Lin, J.; Moquin, R.V.; Shen, Z.; Cook, L.S.; Doweyko, A.M.; Pitt, S.; Pang, S.; Shen, D.R.; Fang, Q.; de Fex, H.F.; McIntyre, K.W.; Shuster, D.J.; Gillooly, K.M.; Behnia, K.; Schieven, G.L.; Wityak, J.; Barrish, J.C. 2-aminothiazole as a novel kinase inhibitor template. Structure-activity relationship studies toward the discovery of N-(2-chloro-6-methylphenyl)-2-[[6-[4-(2-hydroxyethyl)-1- piperazinyl)]-2-methyl-4-pyrimidinyl]amino)]-1,3-thiazole-5-carboxamide (dasatinib, BMS-354825) as a potent pan-Src kinase inhibitor. J. Med. Chem., 2006, 49(23), 6819-6832.
[PMID: 17154512]
[52]
Huang, F.; Reeves, K.; Han, X.; Fairchild, C.; Platero, S.; Wong, T.W.; Lee, F.; Shaw, P.; Clark, E. Identification of candidate molecular markers predicting sensitivity in solid tumors to dasatinib: rationale for patient selection. Cancer Res., 2007, 67(5), 2226-2238.
[PMID: 17332353]
[53]
Finn, R.S.; Bengala, C.; Ibrahim, N.; Roché, H.; Sparano, J.; Strauss, L.C.; Fairchild, J.; Sy, O.; Goldstein, L.J. Dasatinib as a single agent in triple-negative breast cancer: results of an open-label phase 2 study. Clin. Cancer Res., 2011, 17(21), 6905-6913.
[PMID: 22028489]
[54]
Green, T.P.; Fennell, M.; Whittaker, R.; Curwen, J.; Jacobs, V.; Allen, J.; Logie, A.; Hargreaves, J.; Hickinson, D.M.; Wilkinson, R.W.; Elvin, P.; Boyer, B.; Carragher, N.; Plé, P.A.; Bermingham, A.; Holdgate, G.A.; Ward, W.H.J.; Hennequin, L.F.; Davies, B.R.; Costello, G.F. Preclinical anticancer activity of the potent, oral Src inhibitor AZD0530. Mol. Oncol., 2009, 3(3), 248-261.
[PMID: 19393585]
[55]
Chen, Y.; Alvarez, E.A.; Azzam, D.; Wander, S.A.; Guggisberg, N.; Jordà, M.; Ju, Z.; Hennessy, B.T.; Slingerland, J.M. Combined Src and ER blockade impairs human breast cancer proliferation in vitro and in vivo. Breast Cancer Res. Treat., 2011, 128(1), 69-78.
[PMID: 20669046]
[56]
Kenna, M.M.; McGarrigle, S.; Pidgeon, G.P. The next Generation of PI3K-Akt-MTOR Pathway Inhibitors in Breast Cancer Cohorts. Biochimica et Biophysica Acta (BBA) -. Rev. Can., 2018, 1870, 185-197.
[57]
Furet, P.; Guagnano, V.; Fairhurst, R.A.; Imbach-Weese, P.; Bruce, I.; Knapp, M.; Fritsch, C.; Blasco, F.; Blanz, J.; Aichholz, R.; Hamon, J.; Fabbro, D.; Caravatti, G. Discovery of NVP-BYL719 a potent and selective phosphatidylinositol-3 kinase alpha inhibitor selected for clinical evaluation. Bioorg. Med. Chem. Lett., 2013, 23(13), 3741-3748.
[PMID: 23726034]
[58]
Amanda Turney. FDA Approves First PI3K Inhibitor for Breast Cancer.,
[59]
Burger, M.T.; Pecchi, S.; Wagman, A.; Ni, Z-J.; Knapp, M.; Hendrickson, T.; Atallah, G.; Pfister, K.; Zhang, Y.; Bartulis, S.; Frazier, K.; Ng, S.; Smith, A.; Verhagen, J.; Haznedar, J.; Huh, K.; Iwanowicz, E.; Xin, X.; Menezes, D.; Merritt, H.; Lee, I.; Wiesmann, M.; Kaufman, S.; Crawford, K.; Chin, M.; Bussiere, D.; Shoemaker, K.; Zaror, I.; Maira, S-M.; Voliva, C.F. Identification of NVP-BKM120 as a Potent, Selective, Orally Bioavailable Class I PI3 Kinase Inhibitor for Treating Cancer. ACS Med. Chem. Lett., 2011, 2(10), 774-779.
[PMID: 24900266]
[60]
PI3K Inhibitor Improves PFS in BELLE-2 Trial. Cancer Discov., 2016, 6(2), 115-116.
[PMID: 26681740]
[61]
D’Assoro, A.B.; Haddad, T.; Galanis, E. Aurora-A Kinase as a Promising Therapeutic Target in Cancer. Front. Oncol., 2016, 5, 295.
[PMID: 26779440]
[62]
Hole, S.; Pedersen, A.M.; Lykkesfeldt, A.E.; Yde, C.W. Aurora kinase A and B as new treatment targets in aromatase inhibitor-resistant breast cancer cells. Breast Cancer Res. Treat., 2015, 149(3), 715-726.
[PMID: 25667100]
[63]
Cicenas, J. The Aurora kinase inhibitors in cancer research and therapy. J. Cancer Res. Clin. Oncol., 2016, 142(9), 1995-2012.
[PMID: 26932147]
[64]
Li, J.P.; Yang, Y.X.; Liu, Q.L.; Pan, S.T.; He, Z.X.; Zhang, X.; Yang, T.; Chen, X.W.; Wang, D.; Qiu, J.X.; Zhou, S.F. The investigational Aurora kinase A inhibitor alisertib (MLN8237) induces cell cycle G2/M arrest, apoptosis, and autophagy via p38 MAPK and Akt/mTOR signaling pathways in human breast cancer cells. Drug Des. Devel. Ther., 2015, 9, 1627-1652.
[PMID: 25834401]
[65]
Melichar, B.; Adenis, A.; Lockhart, A.C.; Bennouna, J.; Dees, E.C.; Kayaleh, O.; Obermannova, R.; DeMichele, A.; Zatloukal, P.; Zhang, B.; Ullmann, C.D.; Schusterbauer, C. Safety and activity of alisertib, an investigational aurora kinase A inhibitor, in patients with breast cancer, small-cell lung cancer, non-small-cell lung cancer, head and neck squamous-cell carcinoma, and gastro-oesophageal adenocarcinoma: a five-arm phase 2 study. Lancet Oncol., 2015, 16(4), 395-405.
[PMID: 25728526]
[66]
Niu, H.; Manfredi, M.; Ecsedy, J.A. Scientific Rationale Supporting the Clinical Development Strategy for the Investigational Aurora A Kinase Inhibitor Alisertib in Cancer. Front. Oncol., 2015, 5, 189.
[PMID: 26380220]
[67]
Zhou, S-F.; Li, J-P.; Yang, Y.X.; Liu, Q.L.; Zhou, Z.W.; Pan, S.; He, Z.; Zhang, X.; Yang, T.; Pan, S.Y.; Duan, W.; He, S.M.; Chen, X.W.; Qiu, J. The pan-inhibitor of Aurora kinases danusertib induces apoptosis and autophagy and suppresses epithelial-to-mesenchymal transition in human breast cancer cells. Drug Des. Devel. Ther., 2015, 9, 1027-1062.
[68]
Geffken, K.; Spiegel, S. Sphingosine kinase 1 in breast cancer. Adv. Biol. Regul., 2018, 67, 59-65.
[PMID: 29055687]
[69]
Gao, Y.; Gao, F.; Chen, K.; Tian, M.L.; Zhao, D.L. Sphingosine kinase 1 as an anticancer therapeutic target. Drug Des. Devel. Ther., 2015, 9, 3239-3245.
[PMID: 26150697]
[70]
Maczis, M.; Milstien, S.; Spiegel, S. Sphingosine-1-phosphate and estrogen signaling in breast cancer. Adv. Biol. Regul., 2016, 60, 160-165.
[PMID: 26601898]
[71]
Tsuchida, J.; Nagahashi, M.; Nakajima, M.; Moro, K.; Tatsuda, K.; Ramanathan, R.; Takabe, K.; Wakai, T. Breast cancer sphingosine-1-phosphate is associated with phospho-sphingosine kinase 1 and lymphatic metastasis. J. Surg. Res., 2016, 205(1), 85-94.
[PMID: 27621003]
[72]
Martin, J.L.; de Silva, H.C.; Lin, M.Z.; Scott, C.D.; Baxter, R.C. Inhibition of insulin-like growth factor-binding protein-3 signaling through sphingosine kinase-1 sensitizes triple-negative breast cancer cells to EGF receptor blockade. Mol. Cancer Ther., 2014, 13(2), 316-328.
[PMID: 24337110]
[73]
Datta, A.; Loo, S.Y.; Huang, B.; Wong, L.; Tan, S.S.L.; Tan, T.Z.; Lee, S-C.; Thiery, J.P.; Lim, Y.C.; Yong, W.P.; Lam, Y.; Kumar, A.P.; Yap, C.T. SPHK1 regulates proliferation and survival responses in triple-negative breast cancer. Oncotarget, 2014, 5(15), 5920-5933.
[PMID: 25153718]
[74]
Lim, K.G.; Tonelli, F.; Li, Z.; Lu, X.; Bittman, R.; Pyne, S.; Pyne, N.J. FTY720 analogues as sphingosine kinase 1 inhibitors: enzyme inhibition kinetics, allosterism, proteasomal degradation, and actin rearrangement in MCF-7 breast cancer cells. J. Biol. Chem., 2011, 286(21), 18633-18640.
[PMID: 21464128]
[75]
Woo, S.M.; Seo, B.R.; Min, K.J.; Kwon, T.K. FTY720 enhances TRAIL-mediated apoptosis by up-regulating DR5 and down-regulating Mcl-1 in cancer cells. Oncotarget, 2015, 6(13), 11614-11626.
[PMID: 25843953]
[76]
Ingham, M.; Schwartz, G.K. Cell-Cycle Therapeutics Come of Age. J. Clin. Oncol., 2017, 35(25), 2949-2959.
[PMID: 28580868]
[77]
Rossi, L.; McCartney, A.; Risi, E.; De Santo, I.; Migliaccio, I.; Malorni, L.; Biganzoli, L.; Di Leo, A. Cyclin-dependent kinase 4/6 inhibitors in neoadjuvant endocrine therapy of hormone receptor-positive breast cancer. Clin. Breast Cancer, 2019, 19(6), 392-398.
[PMID: 31358432]
[78]
Murphy, C.G.; Dickler, M.N. The role of CDK4/6 inhibition in breast cancer. Oncologist, 2015, 20(5), 483-490.
[PMID: 25876993]
[79]
Asghar, U.; Witkiewicz, A.K.; Turner, N.C.; Knudsen, E.S. The history and future of targeting cyclin-dependent kinases in cancer therapy. Nat. Rev. Drug Discov., 2015, 14(2), 130-146.
[PMID: 25633797]
[80]
Dukelow, T.; Kishan, D.; Khasraw, M.; Murphy, C.G. CDK4/6 inhibitors in breast cancer. Anticancer Drugs, 2015, 26(8), 797-806.
[PMID: 26053278]
[81]
Knudsen, E.S.; Witkiewicz, A.K. The strange case of CDK4/6 inhibitors: mechanisms, resistance, and combination strategies. Trends Cancer, 2017, 3(1), 39-55.
[PMID: 28303264]
[82]
Finn, R.S.; Crown, J.P.; Lang, I.; Boer, K.; Bondarenko, I.M.; Kulyk, S.O.; Ettl, J.; Patel, R.; Pinter, T.; Schmidt, M.; Shparyk, Y.; Thummala, A.R.; Voytko, N.L.; Fowst, C.; Huang, X.; Kim, S.T.; Randolph, S.; Slamon, D.J. The cyclin-dependent kinase 4/6 inhibitor palbociclib in combination with letrozole versus letrozole alone as first-line treatment of oestrogen receptor-positive, HER2-negative, advanced breast cancer (PALOMA-1/TRIO-18): a randomised phase 2 study. Lancet Oncol., 2015, 16(1), 25-35.
[PMID: 25524798]
[83]
Mukai, H.; Shimizu, C.; Masuda, N.; Ohtani, S.; Ohno, S.; Takahashi, M.; Yamamoto, Y.; Nishimura, R.; Sato, N.; Ohsumi, S.; Iwata, H.; Mori, Y.; Hashigaki, S.; Muramatsu, Y.; Nagasawa, T.; Umeyama, Y.; Lu, D.R.; Toi, M. Palbociclib in combination with letrozole in patients with estrogen receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer: PALOMA-2 subgroup analysis of Japanese patients. Int. J. Clin. Oncol., 2019, 24(3), 274-287.
[PMID: 30515674]
[84]
Verma, S.; Bartlett, C.H.; Schnell, P.; DeMichele, A.M.; Loi, S.; Ro, J.; Colleoni, M.; Iwata, H.; Harbeck, N.; Cristofanilli, M.; Zhang, K.; Thiele, A.; Turner, N.C.; Rugo, H.S. Palbociclib in combination with fulvestrant in women with hormone receptor-positive/HER2-negative advanced metastatic breast cancer: detailed safety analysis from a multicenter, randomized, placebo-controlled, phase III study (PALOMA-3). Oncologist, 2016, 21(10), 1165-1175.
[PMID: 27368881]
[85]
Finn, R.S.; Martin, M.; Rugo, H.S.; Jones, S.; Im, S.A.; Gelmon, K.; Harbeck, N.; Lipatov, O.N.; Walshe, J.M.; Moulder, S.; Gauthier, E.; Lu, D.R.; Randolph, S.; Diéras, V.; Slamon, D.J. Palbociclib and Letrozole in Advanced Breast Cancer. N. Engl. J. Med., 2016, 375(20), 1925-1936.
[PMID: 27959613]
[86]
Cristofanilli, M.; Turner, N.C.; Bondarenko, I.; Ro, J.; Im, S.A.; Masuda, N.; Colleoni, M.; DeMichele, A.; Loi, S.; Verma, S.; Iwata, H.; Harbeck, N.; Zhang, K.; Theall, K.P.; Jiang, Y.; Bartlett, C.H.; Koehler, M.; Slamon, D. Fulvestrant plus palbociclib versus fulvestrant plus placebo for treatment of hormone-receptor-positive, HER2-negative metastatic breast cancer that progressed on previous endocrine therapy (PALOMA-3): final analysis of the multicentre, double-blind, phase 3 randomised controlled trial. Lancet Oncol., 2016, 17(4), 425-439.
[PMID: 26947331]
[87]
Infante, J.R.; Cassier, P.A.; Gerecitano, J.F.; Witteveen, P.O.; Chugh, R.; Ribrag, V.; Chakraborty, A.; Matano, A.; Dobson, J.R.; Crystal, A.S.; Parasuraman, S.; Shapiro, G.I. a phase i study of the cyclin-dependent kinase 4/6 inhibitor ribociclib (LEE011) in patients with advanced solid tumors and lymphomas. Clin. Cancer Res., 2016, 22(23), 5696-5705.
[PMID: 27542767]
[88]
O’Shaughnessy, J.; Petrakova, K.; Sonke, G.S.; Conte, P.; Arteaga, C.L.; Cameron, D.A.; Hart, L.L.; Villanueva, C.; Jakobsen, E.; Beck, J.T.; Lindquist, D.; Souami, F.; Mondal, S.; Germa, C.; Hortobagyi, G.N. Ribociclib plus letrozole versus letrozole alone in patients with de novo HR+, HER2- advanced breast cancer in the randomized MONALEESA-2 trial. Breast Cancer Res. Treat., 2018, 168(1), 127-134.
[PMID: 29164421]
[89]
Hortobagyi, G.N.; Stemmer, S.M.; Burris, H.A.; Yap, Y-S.; Sonke, G.S.; Paluch-Shimon, S.; Campone, M.; Blackwell, K.L.; André, F.; Winer, E.P.; Janni, W.; Verma, S.; Conte, P.; Arteaga, C.L.; Cameron, D.A.; Petrakova, K.; Hart, L.L.; Villanueva, C.; Chan, A.; Jakobsen, E.; Nusch, A.; Burdaeva, O.; Grischke, E-M.; Alba, E.; Wist, E.; Marschner, N.; Favret, A.M.; Yardley, D.; Bachelot, T.; Tseng, L-M.; Blau, S.; Xuan, F.; Souami, F.; Miller, M.; Germa, C.; Hirawat, S.; O’Shaughnessy, J. Ribociclib as first-line therapy for hr-positive, advanced breast cancer. N. Engl. J. Med., 2016, 375(18), 1738-1748.
[PMID: 27717303]
[90]
Hortobagyi, G.N.; Stemmer, S.M.; Burris, H.A.; Yap, Y.S.; Sonke, G.S.; Paluch-Shimon, S.; Campone, M.; Petrakova, K.; Blackwell, K.L.; Winer, E.P.; Janni, W.; Verma, S.; Conte, P.F.; Arteaga, C.L.; Cameron, D.A.; Xuan, F.; Miller, M.K.; Germa, C.; Hirawat, S.; O’Shaughnessy, J. Updated Results from MONALEESA-2, a Phase 3 Trial of First-Line Ribociclib + Letrozole in Hormone Receptor-Positive (HR+), HER2-Negative (HER2-), Advanced Breast Cancer (ABC). J. Clin. Oncol., 2017, 35, 1038-1038.
[91]
Slamon, D.J.; Neven, P.; Chia, S.; Fasching, P.A.; De Laurentiis, M.; Im, S.A.; Petrakova, K.; Bianchi, G.V.; Esteva, F.J.; Martín, M.; Nusch, A.; Sonke, G.S.; De la Cruz-Merino, L.; Beck, J.T.; Pivot, X.; Vidam, G.; Wang, Y.; Rodriguez Lorenc, K.; Miller, M.; Taran, T.; Jerusalem, G. Phase III randomized study of ribociclib and fulvestrant in hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer: MONALEESA-3. J. Clin. Oncol., 2018, 36(24), 2465-2472.
[PMID: 29860922]
[92]
Tripathy, D.; Sohn, J. Proceedings of the General Session Abstracts, 2018, pp. GS2-05.
[93]
Dickler, M.N.; Tolaney, S.M.; Rugo, H.S.; Cortés, J.; Diéras, V.; Patt, D.; Wildiers, H.; Hudis, C.A.; O’Shaughnessy, J.; Zamora, E.; Yardley, D.A.; Frenzel, M.; Koustenis, A.; Baselga, J. MONARCH 1, A Phase II Study of Abemaciclib, a CDK4 and CDK6 Inhibitor, as a Single Agent, in Patients with Refractory HR+/HER2- Metastatic Breast Cancer. Clin. Cancer Res., 2017, 23(17), 5218-5224.
[PMID: 28533223]
[94]
Sledge, G.W., Jr; Toi, M.; Neven, P.; Sohn, J.; Inoue, K.; Pivot, X.; Burdaeva, O.; Okera, M.; Masuda, N.; Kaufman, P.A.; Koh, H.; Grischke, E-M.; Frenzel, M.; Lin, Y.; Barriga, S.; Smith, I.C.; Bourayou, N.; Llombart-Cussac, A. MONARCH 2: abemaciclib in combination with fulvestrant in women with HR+/HER2- advanced breast cancer who had progressed while receiving endocrine therapy. J. Clin. Oncol., 2017, 35(25), 2875-2884.
[PMID: 28580882]
[95]
Goetz, M.P.; Toi, M.; Campone, M.; Sohn, J.; Paluch-Shimon, S.; Huober, J.; Park, I.H.; Trédan, O.; Chen, S-C.; Manso, L.; Freedman, O.C.; Garnica Jaliffe, G.; Forrester, T.; Frenzel, M.; Barriga, S.; Smith, I.C.; Bourayou, N.; Di Leo, A. MONARCH 3: abemaciclib as initial therapy for advanced breast cancer. J. Clin. Oncol., 2017, 35(32), 3638-3646.
[PMID: 28968163]
[96]
Zafrakas, M.; Papasozomenou, P.; Emmanouilides, C. Sorafenib in breast cancer treatment: A systematic review and overview of clinical trials. World J. Clin. Oncol., 2016, 7(4), 331-336.
[PMID: 27579253]
[97]
Chinchar, E.; Makey, K.L.; Gibson, J.; Chen, F.; Cole, S.A.; Megason, G.C.; Vijayakumar, S.; Miele, L.; Gu, J-W. Sunitinib significantly suppresses the proliferation, migration, apoptosis resistance, tumor angiogenesis and growth of triple-negative breast cancers but increases breast cancer stem cells. Vasc. Cell, 2014, 6, 12.
[PMID: 24914410]
[98]
Burstein, H.J.; Elias, A.D.; Rugo, H.S.; Cobleigh, M.A.; Wolff, A.C.; Eisenberg, P.D.; Lehman, M.; Adams, B.J.; Bello, C.L.; DePrimo, S.E.; Baum, C.M.; Miller, K.D.; Phase, I.I. Phase II study of sunitinib malate, an oral multitargeted tyrosine kinase inhibitor, in patients with metastatic breast cancer previously treated with an anthracycline and a taxane. J. Clin. Oncol., 2008, 26(11), 1810-1816.
[PMID: 18347007]
[99]
Liljegren, A.; Bergh, J.; Castany, R. Early experience with sunitinib, combined with docetaxel, in patients with metastatic breast cancer. Breast, 2009, 18(4), 259-262.
[PMID: 19744626]
[100]
Bachelot, T.; Garcia-Saenz, J.A.; Verma, S.; Gutierrez, M.; Pivot, X.; Kozloff, M.F.; Prady, C.; Huang, X.; Khosravan, R.; Wang, Z.; Cesari, R.; Tassell, V.; Kern, K.A.; Blay, J-Y.; Lluch, A. Sunitinib in combination with trastuzumab for the treatment of advanced breast cancer: activity and safety results from a phase II study. BMC Cancer, 2014, 14, 166.
[PMID: 24606768]
[101]
Kleibeuker, E.A.; Ten Hooven, M.A.; Verheul, H.M.; Slotman, B.J.; Thijssen, V.L. Combining radiotherapy with sunitinib: lessons (to be) learned. Angiogenesis, 2015, 18(4), 385-395.
[PMID: 26202788]
[102]
Cristofanilli, M.; Johnston, S.R.D.; Manikhas, A.; Gomez, H.L.; Gladkov, O.; Shao, Z.; Safina, S.; Blackwell, K.L.; Alvarez, R.H.; Rubin, S.D.; Ranganathan, S.; Redhu, S.; Trudeau, M.E. A randomized phase II study of lapatinib + pazopanib versus lapatinib in patients with HER2+ inflammatory breast cancer. Breast Cancer Res. Treat., 2013, 137(2), 471-482.
[PMID: 23239151]
[103]
Hu-Lowe, D.D.; Zou, H.Y.; Grazzini, M.L.; Hallin, M.E.; Wickman, G.R.; Amundson, K.; Chen, J.H.; Rewolinski, D.A.; Yamazaki, S.; Wu, E.Y.; McTigue, M.A.; Murray, B.W.; Kania, R.S.; O’Connor, P.; Shalinsky, D.R.; Bender, S.L. Nonclinical antiangiogenesis and antitumor activities of axitinib (AG-013736), an oral, potent, and selective inhibitor of vascular endothelial growth factor receptor tyrosine kinases 1, 2, 3. Clin. Cancer Res., 2008, 14(22), 7272-7283.
[PMID: 19010843]
[104]
Martin, L.P.; Kozloff, M.F.; Herbst, R.S.; Samuel, T.A.; Kim, S.; Rosbrook, B.; Tortorici, M.; Chen, Y.; Tarazi, J.; Olszanski, A.J.; Rado, T.; Starr, A.; Cohen, R.B.; Phase, I. Phase I study of axitinib combined with paclitaxel, docetaxel or capecitabine in patients with advanced solid tumours. Br. J. Cancer, 2012, 107(8), 1268-1276.
[PMID: 22996612]
[105]
Wang, X.; Shi, Y.; Huang, D.; Guan, X. Emerging therapeutic modalities of PARP inhibitors in breast cancer. Cancer Treat. Rev., 2018, 68, 62-68.
[PMID: 29870916]
[106]
Robson, M.; Im, S.A.; Senkus, E.; Xu, B.; Domchek, S.M.; Masuda, N.; Delaloge, S.; Li, W.; Tung, N.; Armstrong, A.; Wu, W.; Goessl, C.; Runswick, S.; Conte, P. Olaparib for Metastatic Breast Cancer in Patients with a Germline BRCA Mutation. N. Engl. J. Med., 2017, 377(6), 523-533.
[PMID: 28578601]
[107]
Vinayak, S.; Tolaney, S.M.; Schwartzberg, L.; Mita, M.; McCann, G.; Tan, A.R.; Wahner-Hendrickson, A.E.; Forero, A.; Anders, C.; Wulf, G.M.; Dillon, P.; Lynce, F.; Zarwan, C.; Erban, J.K.; Zhou, Y.; Buerstatte, N.; Graham, J.R.; Arora, S.; Dezube, B.J.; Telli, M.L. Open-label clinical trial of niraparib combined with pembrolizumab for treatment of advanced or metastatic triple-negative breast cancer. JAMA Oncol., 2019, 5, 1132.
[PMID: 31194225]
[108]
Rugo, H.S.; Olopade, O.I.; DeMichele, A.; Yau, C.; van ’t Veer, L.J.; Buxton, M.B.; Hogarth, M.; Hylton, N.M.; Paoloni, M.; Perlmutter, J.; Symmans, W.F.; Yee, D.; Chien, A.J.; Wallace, A.M.; Kaplan, H.G.; Boughey, J.C.; Haddad, T.C.; Albain, K.S.; Liu, M.C.; Isaacs, C.; Khan, Q.J.; Lang, J.E.; Viscusi, R.K.; Pusztai, L.; Moulder, S.L.; Chui, S.Y.; Kemmer, K.A.; Elias, A.D.; Edmiston, K.K.; Euhus, D.M.; Haley, B.B.; Nanda, R.; Northfelt, D.W.; Tripathy, D.; Wood, W.C.; Ewing, C.; Schwab, R.; Lyandres, J.; Davis, S.E.; Hirst, G.L.; Sanil, A.; Berry, D.A.; Esserman, L.J. Adaptive randomization of veliparib-carboplatin treatment in breast cancer. N. Engl. J. Med., 2016, 375(1), 23-34.
[PMID: 27406347]
[109]
Litton, J.; Rugo, H.; Ettl, J.; Hurvitz, S.; Gonçalves, A.; Lee, K-H.; Fehrenbacher, L.; Yerushalmi, R.; Mina, L.; Martin, M.; Roché, H. Proceedings of the General Session Abstracts, 2018, pp. GS6-07.
[110]
Miller, K.; Tong, Y.; Jones, D.R.; Walsh, T.; Danso, M.A.; Ma, C.X.; Silverman, P.; King, M-C.; Badve, S.S.; Perkins, S.M. Cisplatin with or without rucaparib after preoperative chemotherapy in patients with triple negative breast cancer: final efficacy results of hoosier oncology group BRE09-146. J. Clin. Oncol., 2015, 33, 1082-1082.
[111]
Kittaneh, M.; Montero, A.J.; Glück, S. Molecular profiling for breast cancer: a comprehensive review. Biomarkers Cancer, 2013, 5, BIC.S9455