Identification of synergistic drug combinations using breast cancer patient-derived xenografts
Open accessAbstract
Compared with other breast cancer subtypes, triple-negative breast cancer (TNBC) is associated with relatively poor outcomes due to its metastatic propensity, frequent failure to respond to chemotherapy, and lack of alternative, targeted treatment options, despite decades of major research efforts. Our studies sought to identify promising targeted therapeutic candidates for TNBC through in vitro screening of 1,363 drugs in patient-derived xenograft (PDX) models. Using this approach, we generated a dataset that can be used to assess and compare responses of various breast cancer PDXs to many different drugs. Through a series of further drug screening assays and two-drug combination testing, we identified that the combination of afatinib (epidermal growth factor receptor (EGFR) inhibitor) and YM155 (inhibitor of baculoviral inhibitor of apoptosis repeat-containing 5 (BIRC5; survivin) expression) is synergistically cytotoxic across multiple models of basal-like TNBC and reduces PDX mammary tumor growth in vivo . We found that YM155 reduces EGFR expression in TNBC cells, shedding light on its potential mechanism of synergism with afatinib. Both EGFR and BIRC5 are highly expressed in basal-like PDXs, cell lines, and patients, and high expression of both genes reduces metastasis-free survival, suggesting that co-targeting of these proteins holds promise for potential clinical success in TNBC.
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Most in vivo synergy studies simply compare tumor volume at a single day using t test, or use survival analysis to compare time-to-event between groups.
“Most studies simply compare TV at a single day using t test, or use survival analysis to compare the time-to-event (i.e., time for TV to reach a threshold) between groups (4–6, 23).”
From Statistical Assessment of Drug Synergy from <i>In Vivo</i> Combination Studies Using Mouse Tumor Models (2023) · cites this paper as [23]
The Methods (Statistical analyses; page unavailable) report unpaired t tests for comparisons between in vivo treatment groups, and the Figure 8 caption (Results; page unavailable) displays endpoint significance. The paper does not establish that most studies use this approach; it also lists p-values for all measured timepoints. Its survival analysis concerns patients’ metastasis-free survival, not time for tumor volume to reach a threshold. (LLM, conf=0.83)
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Cites
Molecular portraits of human breast tumours
Perou, C., Sørlie, T., Eisen, M., van de Rijn, M., Jeffrey, S., Rees, C. A., Pollack, J., Ross, D., Johnsen, H., Akslen, L., et al. (2000) · Nature · doi:10.1038/35021093 · Cited by 16,551 · see citing works
Nishimura, R., Osako, T., Nishiyama, Y., Tashima, R., Nakano, M., Fujisue, M., Toyozumi, Y., & Arima, N. (2013) · Oncology · doi:10.1159/000353099 · Cited by 13,239 · see citing works
Comprehensive molecular portraits of human breast tumours
The Cancer Genome Atlas Network (2012) · Nature · doi:10.1038/nature11412 · Cited by 12,129 · see citing works
Sørlie, T., Perou, C., Tibshirani, R., Aas, T., Geisler, S., Johnsen, H., Hastie, T., Eisen, M., van de Rijn, M., Jeffrey, S., et al. (2001) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.191367098 · Cited by 11,695 · see citing works
Gene expression profiling predicts clinical outcome of breast cancer
van 't Veer, L. J., Dai, H., van de Vijver, M. J., He, Y. D., Hart, A. A. M., Mao, M., Peterse, H. L., van der Kooy, K., Marton, M. J., Witteveen, A. T., et al. (2002) · Nature · doi:10.1038/415530a · Cited by 9,536 · see citing works
The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroups
METABRIC Group, Curtis, C., Shah, S. P., Chin, S.-F., Turashvili, G., Rueda, O. M., Dunning, M. J., Speed, D., Lynch, A. G., Samarajiwa, S., et al. (2012) · Nature · doi:10.1038/nature10983 · Cited by 6,097 · see citing works
Drug combination studies and their synergy quantification using the Chou-Talalay method
Chou, T.-C. (2010) · Cancer Research · doi:10.1158/0008-5472.can-09-1947 · Cited by 5,739 · see citing works
Lehmann, B. D., Bauer, J. A., Chen, X., Sanders, M. E., Chakravarthy, A. B., Shyr, Y., & Pietenpol, J. A. (2011) · Journal of Clinical Investigation · doi:10.1172/jci45014 · Cited by 5,592 · see citing works
Chou, T.-C. (2006) · Pharmacological Reviews · doi:10.1124/pr.58.3.10 · Cited by 5,163 · see citing works
Triple-negative breast cancer: clinical features and patterns of recurrence
Dent, R., Trudeau, M., Pritchard, K. I., Hanna, W. M., Kahn, H. K., Sawka, C. A., Lickley, L. A., Rawlinson, E., Sun, P., & Narod, S. A. (2007) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-06-3045 · Cited by 5,091 · see citing works
Supervised Risk Predictor of Breast Cancer Based on Intrinsic Subtypes
Parker, J. S., Mullins, M., Cheang, M. C. U., Leung, S. C. Y., Voduc, D. K., Vickery, T. L., Davies, S. R., Fauron, C. M. ‐., He, X., Hu, Z., et al. (2009) · Journal of Clinical Oncology · doi:10.1200/jco.2008.18.1370 · Cited by 4,737 · see citing works
Ki67 expression in breast cancer
Elkablawy, M. A., Albasri, A. M., Mohammed, R. A., Hussainy, A. S., Nouh, M. M., & Alhujaily, A. S. (2016) · Saudi Medical Journal · doi:10.15537/smj.2016.2.12285 · Cited by 4,382 · see citing works
The Triple Negative Paradox: Primary Tumor Chemosensitivity of Breast Cancer Subtypes
Carey, L., Dees, E. C., Sawyer, L., Gatti, L., Moore, D. T., Collichio, F. A., Ollila, D. W., Sartor, C. I., Graham, M. L., & Perou, C. M. (2007) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-06-1109 · Cited by 2,086 · see citing works
Genes that mediate breast cancer metastasis to the brain
Bos, P. D., Zhang, X. H.-F., Nadal, C., Shu, W., Gomis, R. R., Nguyen, D. X., Minn, A. J., van de Vijver, M. J., Gerald, W. L., Foekens, J. A., et al. (2009) · Nature · doi:10.1038/nature08021 · Cited by 1,863 · see citing works
Deconstructing the third dimension – how 3D culture microenvironments alter cellular cues
Baker, B. M., & Chen, C. S. (2012) · Journal of Cell Science · doi:10.1242/jcs.079509 · Cited by 1,760 · see citing works
Patient-Derived Xenograft Models: An Emerging Platform for Translational Cancer Research
Hidalgo, M. M., Amant, F. C., Biankin, A. V., Budínská, E., Byrne, A. T., Caldas, C., Clarke, R. B., de Jong, S., Jonkers, J., Mælandsmo, G. M., et al. (2014) · Cancer Discovery · doi:10.1158/2159-8290.cd-14-0001 · Cited by 1,759 · see citing works
Lehmann, B. D., Jovanović, B., Chen, X., Estrada, M. V., Johnson, K. N., Shyr, Y., Moses, H. L., Sanders, M. E., & Pietenpol, J. A. (2016) · PLoS ONE · doi:10.1371/journal.pone.0157368 · Cited by 1,440 · see citing works
Gao, H., Korn, J. M., Ferretti, S., Monahan, J. E., Wang, Y., Singh, M., Zhang, C., Schnell, C., Yang, G., Zhang, Y., et al. (2015) · Nature Medicine · doi:10.1038/nm.3954 · Cited by 1,393 · see citing works
Deconstructing the molecular portraits of breast cancer
Prat, A., & Perou, C. M. (2010) · Molecular Oncology · doi:10.1016/j.molonc.2010.11.003 · Cited by 1,345 · see citing works
Patient-derived tumour xenografts as models for oncology drug development
Tentler, J. J., Tan, A. C., Weekes, C. D., Jimeno, A., Leong, S., Pitts, T. M., Arcaroli, J. J., Messersmith, W. A., & Eckhardt, S. G. (2012) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2012.61 · Cited by 1,277 · see citing works
Genome remodelling in a basal-like breast cancer metastasis and xenograft
Ding, L., Ellis, M. J., Li, S., Larson, D. E., Chen, K., Wallis, J. W., Harris, C. C., McLellan, M. D., Fulton, R. S., Fulton, L., et al. (2010) · Nature · doi:10.1038/nature08989 · Cited by 1,134 · see citing works
DeRose, Y. S., Wang, G., Lin, Y.-C., Bernard, P. S., Buys, S. S., Ebbert, M., Factor, R. E., Matsen, C. B., Milash, B. A., Nelson, E. W., et al. (2011) · Nature Medicine · doi:10.1038/nm.2454 · Cited by 1,006 · see citing works
Survivin, cancer networks and pathway-directed drug discovery
Altieri, D. C. (2007) · Nature reviews. Cancer · doi:10.1038/nrc2293 · Cited by 998 · see citing works
Patient-Derived Tumor Xenografts: Transforming Clinical Samples into Mouse Models
Siolas, D., & Hannon, G. J. (2013) · Cancer Research · doi:10.1158/0008-5472.can-13-1069 · Cited by 672 · see citing works
Latent Bone Metastasis in Breast Cancer Tied to Src-Dependent Survival Signals
Zhang, X. H.-F., Wang, Q., Gerald, W. L., Hudis, C. A., Norton, L., Smid, M., Foekens, J. A., & Massagué, J. (2009) · Cancer Cell · doi:10.1016/j.ccr.2009.05.017 · Cited by 663 · see citing works
Nakahara, T., Takeuchi, M., Kinoyama, I., Minematsu, T., Shirasuna, K., Matsuhisa, A., Kita, A., Tominaga, F., Yamanaka, K., Kudoh, M., et al. (2007) · Cancer Research · doi:10.1158/0008-5472.can-07-1343 · Cited by 499 · see citing works
Carey, L. A., Rugo, H. S., Marcom, P. K., Mayer, E. L., Esteva, F. J., Ma, C. X., Liu, M. C., Storniolo, A. M., Rimawi, M. F., Forero-Torres, A., et al. (2012) · Journal of Clinical Oncology · doi:10.1200/jco.2010.34.5579 · Cited by 499 · see citing works
FR901228, a Potent Antitumor Antibiotic, Is a Novel Histone Deacetylase Inhibitor
Nakajima, H., Kim, Y. B., Terano, H., Yoshida, M., & Horinouchi, S. (1998) · Experimental Cell Research · doi:10.1006/excr.1998.4027 · Cited by 484 · see citing works
Zhang, X., Claerhout, S., Prat, A., Dobrolecki, L. E., Petrovic, I., Lai, Q., Landis, M. D., Wiechmann, L., Schiff, R., Giuliano, M., et al. (2013) · Cancer Research · doi:10.1158/0008-5472.can-12-4081 · Cited by 483 · see citing works
Three-dimensional in vitro tumor models for cancer research and drug evaluation
Xu, X., Farach‐Carson, M. C., & Jia, X. (2014) · Biotechnology Advances · doi:10.1016/j.biotechadv.2014.07.009 · Cited by 462 · see citing works
Bruna, A., Rueda, O. M., Greenwood, W., Batra, A. S., Callari, M., Batra, R. N., McNamara, K. L., Sandoval, J. L., Cassidy, J. W., Vidaković, A. T., et al. (2016) · Cell · doi:10.1016/j.cell.2016.08.041 · Cited by 432 · see citing works
A New Model of Patient Tumor-Derived Breast Cancer Xenografts for Preclinical Assays
Marangoni, E., Vincent‐Salomon, A., Auger, N., Degeorges, A., Assayag, F., de Crémoux, P., de Plater, L., Guyader, C., Pinieux, G. D. B. D., Judde, J., et al. (2007) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-07-0078 · Cited by 423 · see citing works
Molecular portraits of breast cancer: tumour subtypes as distinct disease entities
Sørlie, T. (2004) · European Journal of Cancer · doi:10.1016/j.ejca.2004.08.021 · Cited by 416 · see citing works
Baselga, J. M., Gómez, P., Greil, R., Braga, S. A., Climent, M. Á., Wardley, A. M., Kaufman, B., Stemmer, S. M., Pêgo, A., Chan, A., et al. (2013) · Journal of Clinical Oncology · doi:10.1200/jco.2012.46.2408 · Cited by 363 · see citing works
Triple negative breast cancer: Emerging therapeutic modalities and novel combination therapies
Lee, A. E., & Djamgoz, M. B. A. (2017) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2017.11.003 · Cited by 354 · see citing works
Survivin: A molecular biomarker in cancer
Mittal, R., Jaiswal, P. K., & Goel, A. (2015) · The Indian Journal of Medical Research · doi:10.4103/0971-5916.159250 · Cited by 353 · see citing works
Epidermal growth factor receptor as a potential therapeutic target in triple-negative breast cancer
Corkery, B., Crown, J. P., CLYNES, M. M., & O’Donovan, N. (2009) · Annals of Oncology · doi:10.1093/annonc/mdn710 · Cited by 348 · see citing works
Fichtner, I., Rolff, J., Soong, R., Hoffmann, J., Hammer, S., Sommer, A., Becker, M., & Merk, J. (2008) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-08-0138 · Cited by 286 · see citing works
Control of cytomegalovirus lytic gene expression by histone acetylation
Murphy, J. C., Fischle, W., Verdin, E. M., & Sinclair, J. H. (2002) · The EMBO Journal · doi:10.1093/emboj/21.5.1112 · Cited by 231 · see citing works
Genomic analysis identifies unique signatures predictive of brain, lung, and liver relapse
Harrell, J. C., Prat, A., Parker, J. S., Fan, C., He, X., Carey, L., Anders, C. K., Ewend, M. G., & Perou, C. M. (2011) · Breast Cancer Research and Treatment · doi:10.1007/s10549-011-1619-7 · Cited by 228 · see citing works
Self-citationDeRose, Y. S., Gligorich, K. M., Wang, G., Georgelas, A., Bowman, P., Courdy, S., Welm, A. L., & Welm, B. E. (2013) · Current Protocols in Pharmacology · doi:10.1002/0471141755.ph1423s60 · Cited by 227 · see citing works
Triple negative breast cancer: the kiss of death
Jitariu, A.-A., Cîmpean, A. M., Ribatti, D., & Raica, M. (2017) · Oncotarget · doi:10.18632/oncotarget.16938 · Cited by 173 · see citing works
Finn, R. S., Press, M. F., Dering, J., Arbushites, M. C., Koehler, M. T., Oliva, C., Williams, L. S., & Leo, A. D. (2009) · Journal of Clinical Oncology · doi:10.1200/jco.2008.18.1925 · Cited by 164 · see citing works
Targeting EGFR in Triple Negative Breast Cancer
Ueno, N. T., & Zhang, D. (2011) · Journal of Cancer · doi:10.7150/jca.2.324 · Cited by 159 · see citing works
Fichtner, I., Slisow, W., Gill, J. H., Becker, M., Elbe, B., Hillebrand, T., & Bibby, M. (2003) · European Journal of Cancer · doi:10.1016/j.ejca.2003.10.011 · Cited by 154 · see citing works
Proteogenomic integration reveals therapeutic targets in breast cancer xenografts
Huang, K., Li, S., Mertins, P., Cao, S., Gunawardena, H. P., Ruggles, K. V., Mani, D. R., Clauser, K. R., Tanioka, M., Usary, J., et al. (2017) · Nature Communications · doi:10.1038/ncomms14864 · Cited by 146 · see citing works
Positioning of proteasome inhibitors in therapy of solid malignancies
Roeten, M. S. F., Cloos, J. J., & Jansen, G. (2017) · Cancer Chemotherapy and Pharmacology · doi:10.1007/s00280-017-3489-0 · Cited by 143 · see citing works
Survivin and YM155: How faithful is the liaison?
Rauch, A., Hennig, D., Schäfer, C., Wirth, M., Marx, C., Heinzel, T., Schneider, G., & Krämer, O. H. (2014) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2014.01.003 · Cited by 131 · see citing works
CIP2A is a target of bortezomib in human triple negative breast cancer cells
Tseng, L.-M., Liu, C.-Y., Chang, K.-C., Chu, P.-Y., Shiau, C.-W., & Chen, K.-F. (2012) · Breast Cancer Research · doi:10.1186/bcr3175 · Cited by 122 · see citing works
Nabholtz, J., Abrial, C., Mouret‐Reynier, M., Dauplat, M.-M., Weber, B. E., Gligorov, J., Forest, A. M., Trédan, O., Vanlemmens, L., Petit, T., et al. (2014) · Annals of Oncology · doi:10.1093/annonc/mdu183 · Cited by 121 · see citing works
Choi, Y. Y., Lee, J. E., Kim, H., Sim, M. H., Kim, K.-K., Lee, G., Kim, H., An, J. Y., Hyung, W. J., Kim, C. B., et al. (2016) · Scientific Reports · doi:10.1038/srep22172 · Cited by 115 · see citing works
Guerrab, A. E., Bamdad, M., Kwiatkowski, F., Bignon, Y., Penault-Llorca, F. M., & Aubel, C. (2016) · Oncotarget · doi:10.18632/oncotarget.12037 · Cited by 115 · see citing works
Cheng, S. M., Chang, Y.-C., Liu, C. Y., Lee, J. Y. C., Chan, H.-H., Kuo, C.-W., Lin, K. Y., Tsai, S. L., Chen, S.-Y., Li, C., et al. (2014) · British Journal of Pharmacology · doi:10.1111/bph.12935 · Cited by 94 · see citing works
Clemens, M., Gladkov, O. A., Gartner, E. M., Vladimirov, V. I., Crown, J. P., Steinberg, J., Jie, F., & Keating, A. T. (2014) · Breast Cancer Research and Treatment · doi:10.1007/s10549-014-3238-6 · Cited by 79 · see citing works
Yi, Y. W., Hong, W., Kang, H. J., Kim, H. J., Zhao, W., Wang, A., Seong, Y., & Bae, I. (2013) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.12046 · Cited by 76 · see citing works
A Targetable EGFR-Dependent Tumor-Initiating Program in Breast Cancer
Savage, P., Blanchet-Cohen, A., Revil, T., Badescu, D., Saleh, S. M. I., Wang, Y.-C., Zuo, D., Liu, L., Bertos, N., Muñoz-Ramos, V., et al. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.10.015 · Cited by 73 · see citing works
Chen, Y., Yeh, M., Yu, M.-C., Wei, Y.-L., Chen, W.-S., Chen, J.-Y., Shih, C.-Y., Tu, C., Chen, C., Hsia, T., et al. (2013) · Breast Cancer Research · doi:10.1186/bcr3575 · Cited by 71 · see citing works
Okamoto, K., Okamoto, I., Hatashita, E., Kuwata, K., Yamaguchi, H., Kita, A., Yamanaka, K., Ono, M., & Nakagawa, K. (2011) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-11-0638 · Cited by 68 · see citing works
Loss of SLCO1B3 drives taxane resistance in prostate cancer
de Morrée, E. S., Böttcher, R., van Soest, R. J., Aghai, A., de Ridder, C. M., Gibson, A. A., Mathijssen, R. H. J., Burger, H., Wiemer, E. A. C., Sparreboom, A., et al. (2016) · British Journal of Cancer · doi:10.1038/bjc.2016.251 · Cited by 64 · see citing works
Development of Three Human Small Cell Lung Cancer Models in Nude Mice
Fiebig, H., Neumann, H., Henß, H., Koch, H.-G., Kaiser, D., & Arnold, H. (1985) · Recent results in cancer research/Recent Results in Cancer Research · doi:10.1007/978-3-642-82372-5_8 · Cited by 63 · see citing works
Yamanaka, K. (2011) · International Journal of Oncology · doi:10.3892/ijo.2011.1077 · Cited by 62 · see citing works
van Weerden, W. M., Bangma, C. H., & de Wit, R. (2008) · British Journal of Cancer · doi:10.1038/sj.bjc.6604822 · Cited by 60 · see citing works
Wang, X.-K., To, K. K. W., Huang, L.-Y., Xu, J.-H., Yang, K., Wang, F., Huang, Z.-C., Ye, S., & Fu, L. (2014) · Oncotarget · doi:10.18632/oncotarget.2647 · Cited by 59 · see citing works
Spontaneously-forming spheroids as anin vitrocancer cell model for anticancer drug screening
Theodoraki, M. A., Júnior, C. D. O. R., Chantarasriwong, O., Corben, A. D., Theodorakis, E. A., & Alpaugh, M. L. (2015) · Oncotarget · doi:10.18632/oncotarget.4013 · Cited by 57 · see citing works
YM155 Induces EGFR Suppression in Pancreatic Cancer Cells
Na, Y.-S., Yang, S., Kim, S.-M., Jung, K.-A., Moon, J.-H., Shin, J.-S., Yoon, D. H., Hong, Y. S., Ryu, M., Lee, J., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0038625 · Cited by 54 · see citing works
Wang, S., Liu, S., Zhao, B., Yang, F., Wang, Y.-T., Liang, Q., Sun, Y., Liu, Y., Song, Z., Cai, Y., et al. (2015) · Oncotarget · doi:10.18632/oncotarget.4536 · Cited by 54 · see citing works
Faversani, A., Vaira, V., Moro, G. P., Tosi, D., Lopergolo, A., Schultz, D., Rivadeneira, D. B., Altieri, D. C., & Bòsari, S. (2014) · Breast Cancer Research · doi:10.1186/bcr3666 · Cited by 51 · see citing works
Tsuji, K., Kawauchi, S., Saito, S., Furuya, T., Ikemoto, K., Nakao, M., Yamamoto, S., Oka, M., Hirano, T., & Sasaki, K. (2010) · BMC Cancer · doi:10.1186/1471-2407-10-15 · Cited by 50 · see citing works
Layman, R. M., Ruppert, A. S., Lynn, M., Mrózek, E., Ramaswamy, B., Lustberg, M. B., Wesolowski, R., Ottman, S., Carothers, S., Bingman, A. K., et al. (2013) · Cancer Chemotherapy and Pharmacology · doi:10.1007/s00280-013-2112-2 · Cited by 48 · see citing works
YM155 potently triggers cell death in breast cancer cells through an autophagy-NF-kB network
Véquaud, É., Séveno, C., Loussouarn, D., Engelhart, L., Campone, M., Juin, P. P., & Barillé‐Nion, S. (2015) · Oncotarget · doi:10.18632/oncotarget.3638 · Cited by 46 · see citing works
Inhibition of Survivin with YM155 Induces Durable Tumor Response in Anaplastic Thyroid Cancer
Mehta, A. R., Zhang, L., Boufraqech, M., Liu‐Chittenden, Y., Zhang, Y., Patel, D., Davis, S. R., Rosenberg, A. Z., Ylaya, K., Aufforth, R., et al. (2015) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-14-3251 · Cited by 45 · see citing works
Separation of breast cancer and organ microenvironment transcriptomes in metastases
Alzubi, M. A., Turner, T. H., Olex, A. L., Sohal, S. S., Tobin, N. P., García‐Recio, S., Bergh, J. C. S., Hatschek, T., Parker, J. S., Sartorius, C. A., et al. (2019) · Breast Cancer Research · doi:10.1186/s13058-019-1123-2 · Cited by 43 · see citing works
Self-citationEx vivo treatment of prostate tumor tissue recapitulates in vivo therapy response
Zhang, W., van Weerden, W. M., de Ridder, C. M. A., Erkens‐Schulze, S., Schönfeld, E., Meijer, T. G., Kanaar, R., van Gent, D. C., & Nonnekens, J. (2018) · The Prostate · doi:10.1002/pros.23745 · Cited by 41 · see citing works
Chemotherapy of childhood rhabdomyosarcomas growing as xenografts in immune-deprived mice.
Houghton, J. A., Houghton, P. J., & Green, A. A. (1982) · PubMed · Cited by 40 · see citing works
Wang, Y., Zhang, W., He, K., Liu, B., Zhang, L., Zhang, W., Kulkarni, A. B., Zhao, Y., & Sun, Z. (2013) · APOPTOSIS · doi:10.1007/s10495-013-0960-1 · Cited by 39 · see citing works
Cheng, C., Chang, J., Huang, S. C., Lin, H.-C., Ho, A., Lim, K., Chang, C.-C., Huang, L., Chang, Y., Chang, Y.-F., et al. (2017) · PLoS ONE · doi:10.1371/journal.pone.0182149 · Cited by 34 · see citing works
Dai, C.-H., Shu, Y., Chen, P., Wu, J., Zhu, L.-H., Yuan, R., Long, W., Zhu, Y., & Li, J. (2018) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2018.10.015 · Cited by 34 · see citing works
Cheng, X. J., Lin, J., Ding, Y. F., Zhu, L., Ye, J., & Tu, S. P. (2016) · Oncotarget · doi:10.18632/oncotarget.6898 · Cited by 34 · see citing works
Radic-Sarikas, B., Halász, M., Huber, K., Winter, G. E., Tsafou, K. P., Papamarkou, T., Brunak, S., Kölch, W., & Superti‐Furga, G. (2017) · Scientific Reports · doi:10.1038/s41598-017-03129-6 · Cited by 33 · see citing works
Turner, T. H., Alzubi, M. A., Sohal, S. S., Olex, A. L., Dozmorov, M. G., & Harrell, J. C. (2018) · Breast Cancer Research and Treatment · doi:10.1007/s10549-018-4748-4 · Cited by 32 · see citing works
Self-citationShi, Y., Yu, Y., Wang, Z., Wang, H., Bieerkehazhi, S., Zhao, Y., Suzuk, L., & Zhang, H. (2016) · Oncotarget · doi:10.18632/oncotarget.12048 · Cited by 32 · see citing works
An HDAC inhibitor enhances the antitumor activity of a CMV promoter-driven DNA vaccine
Lai, M.-D., Chen, C. S., Yang, C.-R., Yuan, S.-Y., Tsai, J.-J., Cf, T., Wang, C.-C., Yen, M.-C., & Lin, C.-C. (2009) · Cancer Gene Therapy · doi:10.1038/cgt.2009.65 · Cited by 31 · see citing works
Sobande, F., Dušek, L., Matějková, A., Rozkoš, T., Laco, J., & Ryška, A. (2015) · PubMed · Cited by 30 · see citing works
Cheng, C., Chou, K.-F., Wu, C., Su, N.-W., Peng, C., Su, Y.-W., Chang, J., Ho, A., Lin, H., Chen, C. G., et al. (2017) · Lung Cancer · doi:10.1016/j.lungcan.2017.12.017 · Cited by 25 · see citing works
Zhao, X., Puszyk, W. M., Lu, Z., Ostrov, D. A., George, T. J., Robertson, K. D., & Liu, C. (2014) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-14-0229 · Cited by 21 · see citing works
Trichostatin-A enhances adaptive immune responses to DNA vaccination
Vanniasinkam, T., Ertl, H. C. J., & Tang, Q. (2006) · Journal of Clinical Virology · doi:10.1016/j.jcv.2006.04.009 · Cited by 20 · see citing works
Yan, X., & Su, H. (2017) · Medical Science Monitor · doi:10.12659/msm.901643 · Cited by 14 · see citing works
Harbeck, N., Schmidt, M., Harter, P., Possinger, K., Jonat, W., Lück, H., Beckmann, M., Fasching, P. A., Schütte, J., Solca, F., et al. (2009) · Cancer Research · doi:10.1158/0008-5472.sabcs-09-5062 · Cited by 10 · see citing works
Okamoto, K., Okamoto, I., Hatashita, E., Kuwata, K., Yamaguchi, H., Kita, A., Yamanaka, K., Ono, M., & Nakagawa, K. (2012) · Annals of Oncology · doi:10.1016/s0923-7534(20)32199-2 · Cited by 7 · see citing works
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3 of the 92 references couldn’t be matched to a known paper.
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Guillen, K. P., Fujita, M., Butterfield, A. J., Scherer, S. D., Bailey, M. H., Chu, Z., DeRose, Y. S., Zhao, L., Cortes-Sanchez, E., Yang, C.-H., et al. (2022) · Nature Cancer · doi:10.1038/s43018-022-00337-6 · Cited by 416 · see citing works
Cocco, S., Leone, A., Roca, M. S., Lombardi, R., Piezzo, M., Caputo, R., Ciardiello, C., Costantini, S., Bruzzese, F., Sisalli, M. J., et al. (2022) · Journal of Translational Medicine · doi:10.1186/s12967-022-03462-z · Cited by 130 · see citing works
Rodrigues, R. C., Duarte, D., & Vale, N. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23084280 · Cited by 67 · see citing works
Laboratory Models for Investigating Breast Cancer Therapy Resistance and Metastasis
Roarty, K. P., & Echeverria, G. V. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.645698 · Cited by 64 · see citing works
You, K. S., Yi, Y. W., Cho, J., Park, J., & Seong, Y. (2021) · Pharmaceuticals · doi:10.3390/ph14060589 · Cited by 64 · see citing works
Mehraj, U., Aisha, S., Sofi, S., & Mir, M. A. (2022) · Advances in Cancer Biology - Metastasis · doi:10.1016/j.adcanc.2022.100037 · Cited by 58 · see citing works
Duarte, D., Falcão, S. I., Mehdi, I. E., Vilas‐Boas, M., & Vale, N. (2022) · Pharmaceutics · doi:10.3390/pharmaceutics14030511 · Cited by 52 · see citing works
Koedoot, E., Wolters, L., Smid, M., Stoilov, P., Burger, G. A., Herpers, B., Yan, K., Price, L., Martens, J. W. M., Dévédec, S. E. L., et al. (2021) · Scientific Reports · doi:10.1038/s41598-021-86664-7 · Cited by 50 · see citing works
Combinations of Calcitriol with Anticancer Treatments for Breast Cancer: An Update
Mendoza, M. S., García‐Quiroz, J., Dı́az, L., & Garcı́a-Becerra, R. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222312741 · Cited by 45 · see citing works
Survivin in Breast Cancer: A Review
Martínez-Sifuentes, M. A., Bassol‐Mayagoitia, S., Nava-Hernández, M. P., Ruíz-Flores, P., Ramos-Treviño, J., Cruz, J. H.-S., & Hernández‐Ibarra, J. A. (2022) · Genetic Testing and Molecular Biomarkers · doi:10.1089/gtmb.2021.0286 · Cited by 43 · see citing works
Cressey, P., Amrahli, M., So, P., Gedroyc, W. M. W., Wright, M., & Thanou, M. (2021) · Biomaterials · doi:10.1016/j.biomaterials.2021.120758 · Cited by 43 · see citing works
The Transformative Role of 3D Culture Models in Triple-Negative Breast Cancer Research
Bittman-Soto, X. S., Thomas, E. S., Ganshert, M., Mendez‐Santacruz, L. L., & Harrell, J. C. (2024) · Cancers · doi:10.3390/cancers16101859 · Cited by 31 · see citing works
Self-citationEpidermal growth factor receptor mutations in breast Cancer: Therapeutic challenges and way forward
Shetty, S. R., Kar, T., & Das, A. (2024) · Bioorganic Chemistry · doi:10.1016/j.bioorg.2024.108037 · Cited by 29 · see citing works
Mao, B., & Guo, S. (2023) · Cancer Research Communications · doi:10.1158/2767-9764.crc-23-0243 · Cited by 27 · see citing works
Español, A. J., Salem, A. R., Bari, M. D., Cristofaro, I., Sánchez, Y., Tata, A. M., & Sales, M. E. (2020) · PLoS ONE · doi:10.1371/journal.pone.0226450 · Cited by 24 · see citing works
Echeverria, G. V., Cai, S., Tu, Y., Shao, J., Powell, E., Redwood, A. B., Jiang, Y., McCoy, A., Rinkenbaugh, A. L., Lau, R., et al. (2023) · npj Breast Cancer · doi:10.1038/s41523-022-00502-1 · Cited by 22 · see citing works
Rapamycin and trametinib: a rational combination for treatment of NSCLC
Sun, C., Li, Y., Cao, D., Zhou, Y.-F., Zhang, M., & Wang, H. (2021) · International Journal of Biological Sciences · doi:10.7150/ijbs.62752 · Cited by 21 · see citing works
Powell, R. T., Redwood, A. B., Liu, X., Guo, L., Cai, S., Zhou, X., Tu, Y., Zhang, X., Qi, Y., Jiang, Y., et al. (2020) · Scientific Reports · doi:10.1038/s41598-020-74882-4 · Cited by 21 · see citing works
Falcão, S. I., Duarte, D., Diallo, M., Santos, J., Ribeiro, E., Vale, N., & Vilas‐Boas, M. (2023) · Molecules · doi:10.3390/molecules28083393 · Cited by 18 · see citing works
Rashid, N. S., Hairr, N. S., Murray, G. F., Olex, A. L., Leftwich, T. J., Grible, J. M., Reed, J. C., Dozmorov, M. G., & Harrell, J. C. (2021) · Translational Oncology · doi:10.1016/j.tranon.2021.101235 · Cited by 16 · see citing works
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Marcolin, J. C., Lichtenfels, M., Silva, C. A., & de Farias, C. B. (2023) · Current Problems in Cancer · doi:10.1016/j.currproblcancer.2023.100996 · Cited by 13 · see citing works
García‐Quiroz, J., Cárdenas-Ochoa, N., Garcı́a-Becerra, R., Morales-Guadarrama, G., Méndez-Pérez, E. A., Santos‐Cuevas, C., Ramírez-Nava, G., Mendoza, M. S., Prado-Garcı́a, H., Avila, E., et al. (2021) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2021.105979 · Cited by 13 · see citing works
Isoniazid potentiates tigecycline to kill methicillin-resistant Staphylococcus aureus
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Dozmorov, M. G., Marshall, M. A., Rashid, N. S., Grible, J. M., Valentine, A. D., Olex, A. L., Murthy, K., Chakraborty, A., Reyna, J., Figueroa, D. S., et al. (2023) · Scientific Reports · doi:10.1038/s41598-023-32568-7 · Cited by 12 · see citing works
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Cava, C., Pini, S., Taramelli, D., & Castiglioni, I. (2020) · Computational Biology and Chemistry · doi:10.1016/j.compbiolchem.2020.107313 · Cited by 7 · see citing works
Kite-Shaped Molecules Block SARS-CoV-2 Cell Entry at a Post-Attachment Step
Chan, S., Shafi, T., & Ford, R. C. (2021) · Viruses · doi:10.3390/v13112306 · Cited by 7 · see citing works
Yuan, Y., Gao, H., Li, Y., & Jiao, X. (2025) · Journal of Pharmaceutical Analysis · doi:10.1016/j.jpha.2025.101225 · Cited by 6 · see citing works
Stratification of Tamoxifen Synergistic Combinations for the Treatment of ER+ Breast Cancer
Zboril, E. K., Grible, J. M., Boyd, D. C., Hairr, N. S., Leftwich, T. J., Esquivel, M., Duong, A. K., Turner, S. A., Ferreira‐Gonzalez, A., Olex, A. L., et al. (2023) · Cancers · doi:10.3390/cancers15123179 · Cited by 6 · see citing works
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Rashid, N. S., Boyd, D. C., Olex, A. L., Grible, J. M., Duong, A. K., Alzubi, M. A., Altman, J. E., Leftwich, T. J., Valentine, A. D., Hairr, N. S., et al. (2022) · Scientific Reports · doi:10.1038/s41598-022-25541-3 · Cited by 5 · see citing works
Self-citationErkmen, C., Rehman, F., & Mohamad, S. B. (2025) · Spectrochimica Acta Part A Molecular and Biomolecular Spectroscopy · doi:10.1016/j.saa.2025.126602 · Cited by 4 · see citing works
Zhu, Z., Zhao, H., Yang, X., Nie, D., Yang, J., & Han, Z. (2025) · Toxins · doi:10.3390/toxins17110563 · Cited by 3 · see citing works
Triple-Negative Breast Cancer (TNBC): Clinical Features and Therapeutic Targets
Jeyachandran, S., Chandrashekar, K., Ganesan, G., Alagarsamy, L., Subbaraj, G. K., & Kulanthaivel, L. (2022) · Handbook of Animal Models and its Uses in Cancer Research · doi:10.1007/978-981-19-1282-5_41-1 · Cited by 3 · see citing works
Multidisciplinary examples of applications: Papers using the MAL-PD/BD/CI/BI theory/method
Chou, T. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-28874-6.00010-x · Cited by 1 · see citing works
Sivan, S. L., & S, V. C. S. (2021) · Biomolecules · doi:10.3390/biom12010037
Maojing, W., Li, W., Ding, L., & Han, Z. (2021) · International Journal of Pharmaceutical Sciences and Developmental Research · doi:10.17352/ijpsdr.000035
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Self-citationRosenzweig, E., Axelrod, D. E., & Gordon, D. (2025) · PLoS ONE · doi:10.1371/journal.pone.0324141
Cocco, S., Leone, A., Roca, M. S., Lombardi, R., Piezzo, M., Caputo, R., Ciardiello, C., Costantini, S., Bruzzese, F., Sisalli, M. J., et al. (2022) · Figshare · doi:10.6084/m9.figshare.20167998
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Self-citationEI24 suppresses TNBC tumorigenesis by regulating AKT signaling
Nam, T. W., Kim, Y. M., Park, H. M., Na, H., Choi, Y., Ahn, S. G., Bae, S. J., Song, Y., Lee, J. H., Jeong, J., et al. (2026) · Frontiers in Oncology · doi:10.3389/fonc.2026.1884404
- Authors
- Turner, T. H., Alzubi, M. A., & Harrell, J. C.
- Affiliations
- Virginia Commonwealth University (US)
- Corresponding author
- Harrell, J. Chuck
- Venue
- Scientific Reports
- Published
- 2020-01-30
- Volume
- 10
- Issue
- 1
- Pages
- 1493-1493
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC6992640
- OpenAlex
- W3004587468
- Cited by
- 50
- References
- 92
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 5 · 2023: 12 · 2022: 9 · 2021: 13 · 2020: 4
- FWCI
- 3.26
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- U.S. Department of Health & Human Services | NIH | National Cancer Institute (F30CA228393)
- Susan G. Komen (CCR19608826)
- Massey Cancer Center, Virginia Commonwealth University
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Breast Cancer Treatment Studies
- Health Sciences › Medicine › Oncology › HER2/EGFR in Cancer Research
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Keywords
- triple-negative breast cancer, drug synergy, patient-derived xenografts, afatinib, YM155, survivin, EGFR inhibition, basal-like breast cancer, targeted therapy, metastasis-free survival, drug repurposing
- MeSH terms
- Survivin, Afatinib, Animals, Antineoplastic Combined Chemotherapy Protocols, Cell Survival, Dose-Response Relationship, Drug, Drug Screening Assays, Antitumor, Drug Synergism, Female, Humans, Imidazoles, Naphthoquinones, Oligopeptides, Carboplatin, Mice, SCID, Mice, Inbred NOD, Xenograft Model Antitumor Assays, Cell Line, Tumor, Mice, Triple Negative Breast Neoplasms, ErbB Receptors
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