Molecular Insight of Regorafenib Treatment for Colorectal Cancer
Open accessAbstract
Regorafenib is a multi-targeting kinase inhibitor approved for the treatment of metastatic colorectal cancer patients in refractory to standard chemotherapy. Similarly to sorafenib, this agent was originally developed as a RAF1 inhibitor. However, the kinase inhibitory profile is distinct from sorafenib. A broad-spectrum of kinase inhibition induces wide-range drug sensitivity, irrespective of mutation status of major oncogenes. This agent's main therapeutic effects are anti-angiogenesis and the remodeling of tumor microenvironment through several mechanisms of action. The dual blockade of VEGF receptors and TIE2 can lead to both additive anti-angiogenesis effects and the suggestive unique regulation of vessel stability. Additionally, it inhibits molecular escape pathways to VEGF inhibition (e.g., FGF, PIGF, and PDGF signaling), enabling its continuous antiangiogenic effect even in tumors resistant to VEGF inhibitors. Furthermore, regorafenib has the important effect of enhancing anti-tumor immunity via macrophage modulation. Based on this concept, clinical trials have been recently launched for the development of a combination strategy with immune checkpoint inhibitors. Contrary to regorafenib induced clinical benefits and advances in the novel strategy, currently no predictive biomarkers have been identified. In the present review, we revisit and summarize regorafenib's unique mechanisms of action. The review could highlight molecular insights and provide some perspective for the search of predictive biomarkers used in metastatic colorectal cancer patients treated with regorafenib.
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Regorafenib functions through a blockade of VEGF and TIE2, leading to anti-angiogenic effects.
“It functions through a blockade of VEGF and TIE2, leading to anti-angiogenic effects [57].”
From Update on Targeted Therapy and Immunotherapy for Metastatic Colorectal Cancer (2024) · cites this paper as [57]
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Hallmarks of Cancer: The Next Generation
Hanahan, D., & Weinberg, R. A. (2011) · Cell · doi:10.1016/j.cell.2011.02.013 · Cited by 66,590 · see citing works
Comprehensive molecular profiling of lung adenocarcinoma
The Cancer Genome Atlas Research Network (2014) · Nature · doi:10.1038/nature13385 · Cited by 5,732 · see citing works
Tumorigenesis and the angiogenic switch
Bergers, G., & Benjamin, L. E. (2003) · Nature reviews. Cancer · doi:10.1038/nrc1093 · Cited by 3,559 · cited 1× · see citing works
“This process is supported by ANG2 [34].”
Integrated Genomic Characterization of Papillary Thyroid Carcinoma
Agrawal, N., Akbani, R., Aksoy, B. A., Ally, A., Arachchi, H., Asa, S. L., Auman, J. T., Balasundaram, M., Balu, S., Baylin, S. B., et al. (2014) · Cell · doi:10.1016/j.cell.2014.09.050 · Cited by 3,080 · see citing works
Saltz, L. B., Clarke, S., Díaz-Rubio, E., Scheithauer, W., Figer, A., Wong, R., Koski, S., Lichinitser, M., Yang, T.-S., Rivera, F., et al. (2008) · Journal of Clinical Oncology · doi:10.1200/jco.2007.14.9930 · Cited by 2,955 · see citing works
Grothey, A., Cutsem, E. V., Sobrero, A., Siena, S., Falcone, A., Ychou, M., Humblet, Y., Bouché, O., Mineur, L., Barone, C., et al. (2013) · The Lancet · doi:10.1016/s0140-6736(12)61900-x · Cited by 2,895 · see citing works
Self-citationFibroblast growth factor signalling: from development to cancer
Turner, N., & Grose, R. (2010) · Nature Reviews. Cancer · doi:10.1038/nrc2780 · Cited by 2,689 · see citing works
Liquid Biopsies: Genotyping Circulating Tumor DNA
Diaz, L. A., & Bardelli, A. (2014) · Journal of Clinical Oncology · doi:10.1200/jco.2012.45.2011 · Cited by 2,210 · see citing works
Molecular Basis of Colorectal Cancer
Markowitz, S. D., & Bertagnolli, M. M. (2009) · New England Journal of Medicine · doi:10.1056/nejmra0804588 · Cited by 2,052 · see citing works
Heinemann, V., von Weikersthal, L. F., Decker, T., Kiani, A., Vehling-Kaiser, U., Al-Batran, S.-E., Heintges, T., Lerchenmüller, C., Kahl, C., Seipelt, G., et al. (2014) · The Lancet Oncology · doi:10.1016/s1470-2045(14)70330-4 · Cited by 1,740 · see citing works
Casanovas, O., Hicklin, D. J., Bergers, G., & Hanahan, D. (2005) · Cancer Cell · doi:10.1016/j.ccr.2005.09.005 · Cited by 1,621 · see citing works
Wells, S. A., Robinson, B. G., Gagel, R. F., Dralle, H., Fagin, J. A., Santoro, M., Baudin, É., Elisei, R., Jarząb, B., Vasselli, J. R., et al. (2011) · Journal of Clinical Oncology · doi:10.1200/jco.2011.35.5040 · Cited by 1,556 · see citing works
Tumor angiogenesis and vascular normalization: alternative therapeutic targets
Viallard, C., & Larrivée, B. (2017) · Angiogenesis · doi:10.1007/s10456-017-9562-9 · Cited by 1,435 · see citing works
Van Cutsem, E., Tabernero, J., Lakomy, R., Prenen, H., Prausová, J., Macarulla, T., Ruff, P., van Hazel, G. A., Moiseyenko, V., Ferry, D., et al. (2012) · Journal of Clinical Oncology · doi:10.1200/jco.2012.42.8201 · Cited by 1,402 · see citing works
Wilhelm, S. M., Dumas, J., Adnane, L., Lynch, M., Carter, C. A., Schütz, G., Thierauch, K., & Zopf, D. (2011) · International Journal of Cancer · doi:10.1002/ijc.25864 · Cited by 1,355 · see citing works
VEGF-A modulates expression of inhibitory checkpoints on CD8+ T cells in tumors
Voron, T., Colussi, O., Marcheteau, E., Pernot, S., Nizard, M., Pointet, A.-L., Latreche, S., Bergaya, S., Benhamouda, N., Tanchot, C., et al. (2015) · Journal of Experimental Medicine · doi:10.1084/jem.20140559 · Cited by 1,179 · see citing works
Bennouna, J., Sastre, J., Arnold, D., Österlund, P., Greil, R., Van Cutsem, E., von Moos, R., Viéitez, J. M., Bouché, O., Borg, C., et al. (2013) · The Lancet Oncology · doi:10.1016/s1470-2045(12)70477-1 · Cited by 1,166 · see citing works
Rational design of inhibitors that bind to inactive kinase conformations
Liu, Y., & Gray, N. S. (2006) · Nature Chemical Biology · doi:10.1038/nchembio799 · Cited by 1,096 · see citing works
Initial Therapy with FOLFOXIRI and Bevacizumab for Metastatic Colorectal Cancer
Loupakis, F., Cremolini, C., Masi, G., Lonardi, S., Zagonel, V., Salvatore, L., Cortesi, E., Tomasello, G., Ronzoni, M., Spadi, R., et al. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1403108 · Cited by 1,062 · see citing works
The landscape of kinase fusions in cancer
Stransky, N., Cerami, E., Schalm, S., Kim, J. L., & Lengauer, C. (2014) · Nature Communications · doi:10.1038/ncomms5846 · Cited by 968 · see citing works
Tabernero, J., Yoshino, T., Cohn, A. L., Obermannova, R., Bodoky, G., Garcia-Carbonero, R., Ciuleanu, T.-E., Portnoy, D. C., Van Cutsem, E., Grothey, A., et al. (2015) · The Lancet Oncology · doi:10.1016/s1470-2045(15)70127-0 · Cited by 952 · see citing works
Fukuoka, S., Hara, H., Takahashi, N., Kojima, T., Kawazoe, A., Asayama, M., Yoshii, T., Kotani, D., Tamura, H., Mikamoto, Y., et al. (2020) · Journal of Clinical Oncology · doi:10.1200/jco.19.03296 · Cited by 890 · see citing works
Li, J., Qin, S., Xu, R., Yau, T. C. C., Ma, B., Pan, H., Xu, J., Bai, Y., Chi, Y., Wang, L., et al. (2015) · The Lancet Oncology · doi:10.1016/s1470-2045(15)70156-7 · Cited by 813 · see citing works
Anti-PlGF Inhibits Growth of VEGF(R)-Inhibitor-Resistant Tumors without Affecting Healthy Vessels
Fischer, C., Jonckx, B., Mazzone, M., Zacchigna, S., Loges, S., Pattarini, L., Chorianopoulos, E., Liesenborghs, L., Koch, M., Mol, M. D., et al. (2007) · Cell · doi:10.1016/j.cell.2007.08.038 · Cited by 780 · see citing works
Lobov, I. B., Brooks, P. C., & Lang, R. A. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.172161899 · Cited by 676 · cited 1× · see citing works
“ANG2 working as a TIE2 antagonist induces angiogenesis in the presence of VEGF, while leads to vessel regression in the absence of VEGF [33].”
BackgroundTherapeutic targeting of the angiopoietin–TIE pathway
Saharinen, P., Eklund, L., & Alitalo, K. (2017) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2016.278 · Cited by 620 · see citing works
Schmittnaegel, M., Rigamonti, N., Kadioglu, E., Cassará, A., Wyser Rmili, C., Kiialainen, A., Kienast, Y., Mueller, H.-J., Ooi, C.-H., Laoui, D., et al. (2017) · Science Translational Medicine · doi:10.1126/scitranslmed.aak9670 · Cited by 582 · see citing works
Role of Angiopoietin-2 in Vascular Physiology and Pathophysiology
Akwii, R. G., Sajib, M. S., Zahra, F. T., & Mikelis, C. M. (2019) · Cells · doi:10.3390/cells8050471 · Cited by 552 · see citing works
Oh, H., Takagi, H., Suzuma, K., Otani, A., Matsumura, M., & Honda, Y. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.22.15732 · Cited by 499 · see citing works
The Intersection between Tumor Angiogenesis and Immune Suppression
Rahma, O. E., & Hodi, F. S. (2019) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-18-1543 · Cited by 480 · see citing works
Angiopoietin-1 Prevents VEGF-Induced Endothelial Permeability by Sequestering Src through mDia
Gavard, J., Patel, V., & Gutkind, J. S. (2008) · Developmental Cell · doi:10.1016/j.devcel.2007.10.019 · Cited by 409 · see citing works
Targeting RET-driven cancers: lessons from evolving preclinical and clinical landscapes
Drilon, A. E. D. C., Hu, Z. I., Lai, G. G. Y., & Tan, D. S. W. (2017) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2017.175 · Cited by 409 · see citing works
Ebos, J. M. L., Lee, C. R., Christensen, J. G., Mutsaers, A. J., & Kerbel, R. S. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0708148104 · Cited by 368 · see citing works
Kloepper, J., Riedemann, L., Amoozgar, Z., Seano, G., Susek, K., Yu, V., Dalvie, N., Amelung, R. L., Datta, M., Song, J. W., et al. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1525360113 · Cited by 357 · see citing works
Vascular Permeability and Drug Delivery in Cancers
Azzi, S., Hebda, J. K., & Gavard, J. (2013) · Frontiers in Oncology · doi:10.3389/fonc.2013.00211 · Cited by 352 · see citing works
Tabernero, J. M., Lenz, H., Siena, S., Sobrero, A. F., Falcone, A., Ychou, M., Humblet, Y., Bouché, O., Mineur, L., Barone, C., et al. (2015) · The Lancet Oncology · doi:10.1016/s1470-2045(15)00138-2 · Cited by 328 · see citing works
Self-citationBekaii‐Saab, T., Ou, F., Ahn, D. H., Boland, P. M., Ciombor, K. K., Heying, E. N., Dockter, T., Jacobs, N. L., Pasche, B., Cleary, J. M., et al. (2019) · The Lancet Oncology · doi:10.1016/s1470-2045(19)30272-4 · Cited by 287 · see citing works
Self-citationAbou‐Elkacem, L., Arns, S., Brix, G., Gremse, F., Zopf, D., Kiessling, F. M., & Lederle, W. (2013) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-12-1162 · Cited by 283 · see citing works
Tie1 controls angiopoietin function in vascular remodeling and inflammation
Korhonen, E. A., Lampinen, A., Giri, H., Anisimov, A., Kim, M., Allen, B., Fang, S., D’Amico, G., Sipilä, T. J., Lohela, M., et al. (2016) · Journal of Clinical Investigation · doi:10.1172/jci84923 · Cited by 283 · see citing works
The Complex Role of Angiopoietin-2 in the Angiopoietin-Tie Signaling PathwayPreprint
Thurston, G., & Daly, C. (2012) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a006650 · Cited by 267 · see citing works
Rothenberg, M. E., Nusse, Y., Kalisky, T., Lee, J. J., Dalerba, P., Scheeren, F., Lobo, N., Kulkarni, S., Sim, S., Qian, D., et al. (2012) · Gastroenterology · doi:10.1053/j.gastro.2012.02.006 · Cited by 263 · see citing works
Pathways Mediating Resistance to Vascular Endothelial Growth Factor–Targeted Therapy
Ellis, L. M., & Hicklin, D. J. (2008) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-07-5287 · Cited by 257 · see citing works
Zhao, P., Wang, Y., Kang, X., Wu, A., Yin, W., Tang, Y., Wang, J., Zhang, M., Duan, Y., & Huang, Y. (2018) · Chemical Science · doi:10.1039/c7sc04853j · Cited by 249 · see citing works
Self-citationRole of Angiopoietin-2 in Adaptive Tumor Resistance to VEGF Signaling Blockade
Rigamonti, N., Kadioglu, E., Keklikoglou, I., Wyser Rmili, C., Leow, C. C., & De Palma, M. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.06.059 · Cited by 247 · see citing works
Opposing actions of angiopoietin-2 on Tie2 signaling and FOXO1 activation
Kim, M., Allen, B. M., Korhonen, E. A., Nitschké, M., Yang, H. W., Bałuk, P., Saharinen, P., Alitalo, K. K., Daly, C., Thurston, G., et al. (2016) · Journal of Clinical Investigation · doi:10.1172/jci84871 · Cited by 245 · see citing works
Falcón, B. L., Hashizume, H., Koumoutsakos, P., Chou, J., BREADY, J. V., Coxon, A., Oliner, J. D., & McDonald, D. M. (2009) · American Journal Of Pathology · doi:10.2353/ajpath.2009.090391 · Cited by 225 · see citing works
Coffelt, S. B., Chen, Y.-Y., Muthana, M., Welford, A. F., Tal, A. O., Scholz, A., Plate, K. H., Reiss, Y., Murdoch, C., De Palma, M., et al. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1002802 · Cited by 220 · see citing works
Cancer-Associated Fibroblasts Connect Metastasis-Promoting Communication in Colorectal Cancer
Tommelein, J., Verset, L., Boterberg, T., Demetter, P., Bracke, M., & Wever, O. D. (2015) · Frontiers in Oncology · doi:10.3389/fonc.2015.00063 · Cited by 207 · see citing works
Goede, V., Coutelle, O., Neuneier, J., Reinacher-Schick, A. C., Schnell, R., Koslowsky, T. C., Weihrauch, M. R., Cremer, B., Kashkar, H., Odenthal, M., et al. (2010) · British Journal of Cancer · doi:10.1038/sj.bjc.6605925 · Cited by 186 · see citing works
McCarty, M. F., Somcio, R., Stoeltzing, O., et al. (2007) · Journal of Clinical Investigation · doi:10.1172/jci31334 · Cited by 175 · see citing works
Savant, S., Porta, S. L., Budnik, A., Busch, K., Hu, J., Tisch, N., Korn, C., Valls, A. F., Benest, A. V., Terhardt, D., et al. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.08.024 · Cited by 172 · see citing works
Van Cutsem, E., Martinelli, E., Cascinu, S., Sobrero, A., Banzi, M., Seitz, J.-F., Barone, C., Ychou, M., Peeters, M., Brenner, B., et al. (2019) · The Oncologist · doi:10.1634/theoncologist.2018-0072 · Cited by 142 · see citing works
Effects of Anti-VEGF Treatment Duration on Tumor Growth, Tumor Regrowth, and Treatment Efficacy
Bagri, A., Berry, L., Gunter, B., Singh, M., Kasman, I. M., Damico, L. A., Xiang, H., Schmidt, M., Fuh, G., Hollister, B. A., et al. (2010) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-09-3100 · Cited by 140 · see citing works
The Role of PDGFs and PDGFRs in Colorectal Cancer
Manzat-Saplacan, R. M., Bălăcescu, L., Gherman, C. D., Chira, R. I., Anca, C., Mircea, P. A., Lisencu, C. I., & Bălăcescu, O. (2017) · Mediators of Inflammation · doi:10.1155/2017/4708076 · Cited by 133 · see citing works
Adenis, A., de la Fouchardière, C., Paule, B., Burtin, P. C., Tougeron, D., Wallet, J., Dourthe, L.-M., Etienne, P.-L., Mineur, L., Clisant, S., et al. (2016) · BMC Cancer · doi:10.1186/s12885-016-2440-9 · Cited by 129 · see citing works
Regorafenib Promotes Antitumor Immunity via Inhibiting PD-L1 and IDO1 Expression in Melanoma
Wu, R.-Y., Kong, P., Xia, L.-P., Huang, Y., Li, Z., Tang, Y.-Y., Chen, Y.-H., Li, X., Senthilkumar, R., Zhang, H., et al. (2019) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-18-2840 · Cited by 116 · see citing works
Identification and characterization of RET fusions in advanced colorectal cancer
Rolle, A.-F. L., Klempner, S. J., Garrett, C. R., Seery, T. E., Sanford, E. M., Balasubramanian, S., Ross, J. S., Stephens, P. J., Miller, V. A., Ali, S. M., et al. (2015) · Oncotarget · doi:10.18632/oncotarget.4325 · Cited by 109 · see citing works
RET fusions in a small subset of advanced colorectal cancers at risk of being neglected
Pietrantonio, F., Nicolantonio, F. D., Schrock, A. B., Lee, J., Morano, F., Fucà, G., Nikolinakos, P. G., Drilon, A. E. D. C., Hechtman, J. F., Christiansen, J., et al. (2018) · Annals of Oncology · doi:10.1093/annonc/mdy090 · Cited by 108 · see citing works
Eisen, T. G., Joensuu, H., Nathan, P., Harper, P., Wojtukiewicz, M. Z., Nicholson, S., Bahl, A. K., Tomczak, P., Pyrhönen, S. O., Fife, K. M., et al. (2012) · The Lancet Oncology · doi:10.1016/s1470-2045(12)70364-9 · Cited by 105 · see citing works
Porta, S. L., Roth, L., Singhal, M., Mogler, C., Spegg, C., Schieb, B., Qu, X., Adams, R. H., Baldwin, H. S., Savant, S., et al. (2018) · Journal of Clinical Investigation · doi:10.1172/jci94674 · Cited by 97 · see citing works
Grothey, A. F., George, S., Cutsem, E. V., et al. (2014) · The Oncologist · doi:10.1634/theoncologist.2013-0059 · Cited by 80 · see citing works
Targeting RET-rearranged non-small-cell lung cancer: future prospects
Bronte, G., Ulivi, P., Verlicchi, A., Cravero, P., Delmonte, A., & Crinò, L. (2019) · Lung Cancer Targets and Therapy · doi:10.2147/lctt.s192830 · Cited by 74 · see citing works
Khan, K. H., Rata, M., Cunningham, D., Koh, D., Tunariu, N., Hahne, J. C., Vlachogiannis, G., Hedayat, S., Marchetti, S., Lampis, A., et al. (2017) · Gut · doi:10.1136/gutjnl-2017-314178 · Cited by 72 · see citing works
Fukuoka, S., Hara, H., Takahashi, N., Kojima, T., Kawazoe, A., Asayama, M., Yoshii, T., Kotani, D., Tamura, H., Mikamoto, Y., et al. (2019) · Journal of Clinical Oncology · doi:10.1200/jco.2019.37.15_suppl.2522 · Cited by 69 · see citing works
Wong, A. L. A., Lim, J. S. J., Sinha, A. K., Gopinathan, A., Lim, R. S. C., Tan, C., Soh, I., Venkatesh, S. K., Titin, C., Sapari, N. S., et al. (2015) · Journal of Translational Medicine · doi:10.1186/s12967-015-0405-4 · Cited by 67 · see citing works
Reprogramming Tumor Blood Vessels for Enhancing Immunotherapy
Schmittnaegel, M., & Palma, M. D. (2017) · Trends in cancer · doi:10.1016/j.trecan.2017.10.002 · Cited by 56 · see citing works
Sunakawa, Y., Furuse, J., Okusaka, T., et al. (2013) · Investigational New Drugs · doi:10.1007/s10637-013-9953-8 · Cited by 55 · see citing works
Argilés, G., Saunders, M. P., Rivera, F., Sobrero, A. F., Benson, A. B., Guillén‐Ponce, C., Cascinu, S., Cutsem, E. V., Macpherson, I. R., Strumberg, D., et al. (2015) · European Journal of Cancer · doi:10.1016/j.ejca.2015.02.013 · Cited by 54 · see citing works
Singh, H., Hansen, T. M., Patel, N. R., & Brindle, N. P. J. (2012) · PLoS ONE · doi:10.1371/journal.pone.0029319 · Cited by 50 · see citing works
Hoff, S., Grünewald, S., Röse, L., & Zopf, D. (2017) · Annals of Oncology · doi:10.1093/annonc/mdx376.060 · Cited by 50 · see citing works
Suenaga, M., Mashima, T., Kawata, N., Wakatsuki, T., Horiike, Y., Matsusaka, S., Dan, S., Shinozaki, E., Seimiya, H., Mizunuma, N., et al. (2016) · Oncotarget · doi:10.18632/oncotarget.9187 · Cited by 46 · see citing works
Tie1: an orphan receptor provides context for angiopoietin-2/Tie2 signaling
Mueller, S. B., & Kontos, C. D. (2016) · Journal of Clinical Investigation · doi:10.1172/jci89963 · Cited by 45 · see citing works
Chen, E. C., Karl, T. A., Tomer Kalisky, C., Gupta, S. K., O'Brien, C. A., Longacre, T. A., van de Rijn, M., Quake, S. R., Clarke, M. F., & Rothenberg, M. E. (2015) · Gastroenterology · doi:10.1053/j.gastro.2015.05.042 · Cited by 43 · see citing works
The preclinical development of regorafenib for the treatment of colorectal cancer
Miura, K., Satoh, M., Kinouchi, M., et al. (2014) · Expert Opinion on Drug Discovery · doi:10.1517/17460441.2014.924923 · Cited by 40 · see citing works
Sanoff, H. K., Goldberg, R. M., Ivanova, A., O’Reilly, S., Kasbari, S. S., Kim, R. D., McDermott, R., Moore, D. T., Zamboni, W. C., Grogan, W. M., et al. (2018) · Cancer · doi:10.1002/cncr.31552 · Cited by 38 · see citing works
Immunohistochemical Staining for c-Kit (CD117) Is a Rare Event in Human Colorectal Carcinoma
Reed, J., Ouban, A., Schickor, F. K., Muraca, P. J., Yeatman, T. J., & Coppola, D. (2002) · Clinical Colorectal Cancer · doi:10.3816/ccc.2002.n.018 · Cited by 37 · see citing works
Vandeputte, C., Kehagias, P., Housni, H. E., Ameye, L., Laes, J., Desmedt, C., Sotiriou, C. P., Deleporte, A., Puleo, F., Geboes, K. P., et al. (2018) · Oncotarget · doi:10.18632/oncotarget.24879 · Cited by 34 · see citing works
Suenaga, M., Schirripa, M., Cao, S., et al. (2018) · Clinical Colorectal Cancer · doi:10.1016/j.clcc.2018.02.010 · Cited by 32 · see citing works
Giampieri, R., Salvatore, L., Prete, M. D., Prochilo, T., D’Anzeo, M., Loretelli, C., Loupakis, F., Aprile, G., Maccaroni, E., Andrikou, K., et al. (2016) · Scientific Reports · doi:10.1038/srep25195 · Cited by 30 · see citing works
Teufel, M., Schwenke, S., Seidel, H., Beckmann, G., Reischl, J., Vonk, R., Lenz, H.-J., Tabernero, J., Siena, S., Grothey, A., et al. (2015) · Journal of Clinical Oncology · doi:10.1200/jco.2015.33.15_suppl.3558 · Cited by 26 · see citing works
Self-citationOliveira, D. M., Grillone, K., Mignogna, C., Falco, V. D., Laudanna, C., Biamonte, F., Locane, R., Corcione, F., Fabozzi, M., Sacco, R., et al. (2018) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-018-0746-y · Cited by 26 · see citing works
Multiple Effects of Angiopoietin-2 Blockade on Tumors
Lewis, C. E., & Ferrara, N. (2011) · Cancer Cell · doi:10.1016/j.ccr.2011.03.016 · Cited by 23 · see citing works
c-Kit as a Novel Potential Therapeutic Target in Colorectal Cancer
Shah, Y. M., & BRINK, G. R. V. D. (2015) · Gastroenterology · doi:10.1053/j.gastro.2015.07.027 · Cited by 19 · see citing works
Lange, F., Franz, B., Maletzki, C., et al. (2014) · BioMed Research International · doi:10.1155/2014/568693 · Cited by 18 · see citing works
Schulz, H., Janßen, J., Strauss, U. P., et al. (2018) · Journal of Clinical Oncology · doi:10.1200/jco.2018.36.4_suppl.748 · Cited by 17 · see citing works
c-Kit Proto-Oncogene Product Is Rarely Detected in Colorectal Adenocarcinoma
Yorke, R. F., Chirala, M., & Younes, M. (2003) · Journal of Clinical Oncology · doi:10.1200/jco.2003.99.213 · Cited by 16 · see citing works
Clarke, J. M., Hurwitz, H. I., & Rangwala, F. A. (2014) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2014.07.001 · Cited by 15 · see citing works
Komatsu, Y., Muro, K., Yamaguchi, K., et al. (2017) · Journal of Clinical Oncology · doi:10.1200/jco.2017.35.4_suppl.721 · Cited by 14 · see citing works
Alfonso, P. G., Benavides, M., Falcó, E., Martín, A. J. M., Gómez, A., Sastre, J., Rivera, F., Montagut, C. O., Salgado, M., López-Ladrón, A., et al. (2018) · The Oncologist · doi:10.1634/theoncologist.2018-0316 · Cited by 12 · see citing works
Schulz, H., Janßen, J., Strauss, U. P., et al. (2017) · Journal of Clinical Oncology · doi:10.1200/jco.2017.35.4_suppl.769 · Cited by 10 · see citing works
Teufel, M., Kalmus, J., Rutstein, M. D., et al. (2016) · Journal of Clinical Oncology · doi:10.1200/jco.2016.34.4_suppl.672 · Cited by 9 · see citing works
Lambrechts, D., Köchert, K., Schulz, A. L., et al. (2016) · Annals of Oncology · doi:10.1093/annonc/mdw200.03 · Cited by 8 · see citing works
Juan, M. O., Öhler, L., Scheithauer, W., et al. (2017) · Annals of Oncology · doi:10.1093/annonc/mdx263.024 · Cited by 8 · see citing works
Köchert, K., Beckmann, G., & Teufel, M. (2017) · Annals of Oncology · doi:10.1093/annonc/mdx393.060 · Cited by 7 · see citing works
Ducreux, M. P., Pétersen, L. N., Öhler, L., et al. (2019) · Journal of Clinical Oncology · doi:10.1200/jco.2019.37.4_suppl.539 · Cited by 6 · see citing works
Suenaga, M., Schirripa, M., Cao, S., et al. (2018) · Journal of Clinical Oncology · doi:10.1200/jco.2018.36.4_suppl.692 · Cited by 3 · see citing works
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Update on Targeted Therapy and Immunotherapy for Metastatic Colorectal Cancer
Underwood, P. W., Ruff, S. M., & Pawlik, T. M. (2024) · Cells · doi:10.3390/cells13030245 · Cited by 130 · see citing works
Li, Y., Chen, X., Li, W., Ye, Y., Du, X., Sun, S., Liu, L., & Zhang, H. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.684309 · Cited by 24 · see citing works
- Authors
- Arai, H., Battaglin, F., Wang, J., Lo, J. H., Soni, S., Zhang, W., & Lenz, H.-J.
- Affiliations
- University of Southern California (US)
- Corresponding author
- Battaglin, Francesca
- Wang, Jingyuan
- Lo, Jae Ho
- Zhang, Wu
- Lenz, Heinz-Josef
- Venue
- Cancer Treatment Reviews
- Publisher
- Elsevier BV
- Published
- 2019-12
- Volume
- 81
- Pages
- 101912
- ISSN
- 0305-7372 (ISSN-L)
- PMC
- PMC7491975
- OpenAlex
- W2982376008
- Cited by
- 191
- References
- 96
- Citations by year
- 2026: 15 · 2025: 22 · 2024: 51 · 2023: 30 · 2022: 28 · 2021: 32 · 2020: 13
- FWCI
- 1.74
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Cancer Treatment Reviews (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (P30CA014089)
- Dhont Family Foundation
- Topics
- Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Keywords
- regorafenib, metastatic colorectal cancer, multikinase inhibitor, angiogenesis inhibition, VEGF receptor blockade, Tie2, tumor microenvironment, FGF signaling, PDGF signaling, tumor-associated macrophages, antitumor immunity, immune checkpoint inhibitors, predictive biomarkers, Raf-1
- MeSH terms
- Antineoplastic Agents, Antineoplastic Combined Chemotherapy Protocols, Humans, Macrophages, Mutation, Phenylurea Compounds, Pyridines, Biomarkers, Tumor, Colorectal Neoplasms, ras Proteins, Angiogenesis Inhibitors, Receptors, Vascular Endothelial Growth Factor, Receptor, TIE-2, Proto-Oncogene Proteins B-raf
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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