The DOI matches its Crossref record; 59 of the 61 references it cites were found in a registry or an index.
Inhibition of Discoidin Domain Receptor 1 Reduces Collagen-mediated Tumorigenicity in Pancreatic Ductal Adenocarcinoma
Open accessPublished version of a preprint
Abstract
The extracellular matrix (ECM), a principal component of pancreatic ductal adenocarcinoma (PDA), is rich in fibrillar collagens that facilitate tumor cell survival and chemoresistance. Discoidin domain receptor 1 (DDR1) is a receptor tyrosine kinase that specifically binds fibrillar collagens and has been implicated in promoting cell proliferation, migration, adhesion, ECM remodeling, and response to growth factors. We found that collagen-induced activation of DDR1 stimulated protumorigenic signaling through protein tyrosine kinase 2 (PYK2) and pseudopodium-enriched atypical kinase 1 (PEAK1) in pancreatic cancer cells. Pharmacologic inhibition of DDR1 with an ATP-competitive orally available small-molecule kinase inhibitor (7rh) abrogated collagen-induced DDR1 signaling in pancreatic tumor cells and consequently reduced colony formation and migration. Furthermore, the inhibition of DDR1 with 7rh showed striking efficacy in combination with chemotherapy in orthotopic xenografts and autochthonous pancreatic tumors where it significantly reduced DDR1 activation and downstream signaling, reduced primary tumor burden, and improved chemoresponse. These data demonstrate that targeting collagen signaling in conjunction with conventional cytotoxic chemotherapy has the potential to improve outcome for pancreatic cancer patients. Mol Cancer Ther; 16(11); 2473–85. ©2017 AACR.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“PDAC cells produce “tonic” (low) levels of a distinct oncogenic homo-trimeric collagen that binds to α3β1 integrin, thereby mediating immune suppression and reprogramming the tumor-associated microbiome167”
From Pancreatic cancer: Advances and challenges (2023) · cites this paper as [167]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
1 retracted
DDR1 Receptor Tyrosine Kinase Promotes Prosurvival Pathway through Notch1 Activation
Kim, H.-G., Hwang, S.-Y., Aaronson, S. A., Mandinova, A., & Lee, S. W. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.236612 · Cited by 94 · cited 1×
“DDR1 inhibition has also been shown to reduce tumorigenicity in multiple tumor models (23, 25, 51, 52).”
BackgroundRetractedKalluri, R., & Zeisberg, M. (2006) · Nature Reviews Cancer · doi:10.1038/nrc1877 · Cited by 4,538 · cited 1×
“Collagen is expressed in PDA by stromal cells, mainly fibroblasts, with a relatively minor but functionally relevant contribution by tumor cells (18, 19).”
BackgroundSomatic mutations affect key pathways in lung adenocarcinoma
Ding, L., Getz, G., Wheeler, D. A., Mardis, E. R., McLellan, M. D., Cibulskis, K., Sougnez, C., Greulich, H., Muzny, D. M., Morgan, M. B., et al. (2008) · Nature · doi:10.1038/nature07423 · Cited by 2,681 · cited 1×
“Dasatinib in particular has demonstrated promising therapeutic efficacy in lung cancer cells (57) and squamous cell carcinoma patients (58) harboring gain-of-function DDR2 mutations.”
BackgroundHingorani, S. R., Wang, L., Multani, A. S., Combs, C., Deramaudt, T. B., Hruban, R. H., Rustgi, A. K., Chang, S., & Tuveson, D. A. (2005) · Cancer Cell · doi:10.1016/j.ccr.2005.04.023 · Cited by 2,609
Collagen density promotes mammary tumor initiation and progression
Provenzano, P. P., Inman, D. R., Eliceiri, K. W., Knittel, J. G., Yan, L., Rueden, C., White, J. G., & Keely, P. J. (2008) · BMC Medicine · doi:10.1186/1741-7015-6-11 · Cited by 1,394
Hoff, D. D. V., Ramanathan, R. K., Borad, M. J., Laheru, D. A., Smith, L. S., Wood, T. E., Korn, R. L., Desai, N. P., Trieu, V. N., Iglesias, J. L. M., et al. (2011) · Journal of Clinical Oncology · doi:10.1200/jco.2011.36.5742 · Cited by 1,040 · cited 1×
“In addition, it was reported that the restoration of SPARC expression enhanced radiosensitivity and chemosensitivity in preclinical models of colon cancer (45) and that SPARC expression enhanced chemoresponse in cancer patients (46, 47).”
BackgroundChauhan, V. P., Martin, J. D., Liu, H., Lacorre, D. A., Jain, S. R., Kozin, S. V., Stylianopoulos, T., Mousa, A. S., Han, X., Adstamongkonkul, P., et al. (2013) · Nature Communications · doi:10.1038/ncomms3516 · Cited by 1,031 · cited 1×
“These data support the premise that collagen-mediated activation of DDR1 induces a signal pathway that includes PEAK1, SRC, and PYK2, which in turn are potentially responsible for collagen-induced chemoresistance (3, 39) and tumor progression.”
BackgroundThe Discoidin Domain Receptor Tyrosine Kinases Are Activated by Collagen
Vogel, W., Gish, G. D., Alves, F., & Pawson, T. (1997) · Molecular Cell · doi:10.1016/s1097-2765(00)80003-9 · Cited by 1,002 · cited 1×
“The DDR family includes DDR1 and DDR2, which are closely related collagen-specific receptor tyrosine kinases (RTK) that recognize and bind several types of collagen (5-7).”
BackgroundKadler, K. E., Baldock, C., Bella, J., & Boot-Handford, R. (2007) · Journal of Cell Science · doi:10.1242/jcs.03453 · Cited by 887 · cited 1×
“The DDR family includes DDR1 and DDR2, which are closely related collagen-specific receptor tyrosine kinases (RTK) that recognize and bind several types of collagen (5-7).”
BackgroundFuruyama, K., Kawaguchi, Y., Akiyama, H., Horiguchi, M., Kodama, S., Kuhara, T., Hosokawa, S., Elbahrawy, A., Soeda, T., Koizumi, M., et al. (2010) · Nature Genetics · doi:10.1038/ng.722 · Cited by 841 · cited 3×
“Sox9 is expressed in the malignant epithelium and is confined to the duct-like cells; differentiated acinar and endocrine cells do not express Sox9 (36, 37).”
BackgroundRix, U., Hantschel, O. D., Dürnberger, G., Rix, L. L. R., Planyavsky, M., Fernbach, N. V., Kaupe, I., Bennett, K. L., Valent, P., Colinge, J., et al. (2007) · Blood · doi:10.1182/blood-2007-07-102061 · Cited by 671 · cited 1×
“22 Several small molecule inhibitors (imatinib, nilotinib, and dasatinib) that target breakpoint cluster region-Abelson kinase (BCR-ABL) also potently inhibit DDR1/DDR2 activity (53,54).”
BackgroundTumor-stroma interactions in pancreatic ductal adenocarcinoma
Mahadevan, D., & Hoff, D. D. V. (2007) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-06-0686 · Cited by 619 · cited 3×
“This is consistent with reports that collagen signaling is associated with chemoresistance in PDA cell lines (3, 48) and that DDR1 confers resistance to chemotherapy and mediates prosurvival signals (20, 21, 49).”
BackgroundSrc protein-tyrosine kinase structure, mechanism, and small molecule inhibitors
Roskoski, R. J. (2015) · Pharmacological Research · doi:10.1016/j.phrs.2015.01.003 · Cited by 611 · cited 1×
“the potential activity of imatinib and vinorelbine in a phase I/II trial in metastatic breast cancer patients (55), as well as dasatinib in numerous clinical trials in solid tumors (56), could be due in part to the inhibition of DDRs.”
BackgroundDesmoplastic Reaction in Pancreatic Cancer: Role of Pancreatic Stellate Cells
Apte, M. V., Park, S., Phillips, P. A., Santucci, N., Goldstein, D., Kumar, R. K., Ramm, G. A., Buchler, M., Friess, H., McCarroll, J. A., et al. (2004) · Pancreas · doi:10.1097/00006676-200410000-00002 · Cited by 591 · cited 1×
“Collagen is expressed in PDA by stromal cells, mainly fibroblasts, with a relatively minor but functionally relevant contribution by tumor cells (18, 19).”
BackgroundAn Orphan Receptor Tyrosine Kinase Family Whose Members Serve as Nonintegrin Collagen Receptors
Shrivastava, A., Radziejewski, C. H., Campbell, E. B., Kovac, L., McGlynn, M., RYAN, T. E., Davis, S., Goldfarb, M. P., Glass, D. J., Lemke, G., et al. (1997) · Molecular Cell · doi:10.1016/s1097-2765(00)80004-0 · Cited by 543 · cited 1×
“The DDR family includes DDR1 and DDR2, which are closely related collagen-specific receptor tyrosine kinases (RTK) that recognize and bind several types of collagen (5-7).”
BackgroundErkan, M., Michalski, C. W., Rieder, S., Reiser–Erkan, C., Abiatari, I., Kolb, A., Giese, N. A., Esposito, I., Frieß, H., & Kleeff, J. H. (2008) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2008.05.006 · Cited by 433 · cited 1×
“This is consistent with reports that collagen signaling is associated with chemoresistance in PDA cell lines (3, 48) and that DDR1 confers resistance to chemotherapy and mediates prosurvival signals (20, 21, 49).”
BackgroundDiscoidin Domain Receptor Functions in Physiological and Pathological Conditions
Leitinger, B. (2014) · International review of cytology · doi:10.1016/b978-0-12-800180-6.00002-5 · Cited by 401 · cited 2×
“The downstream effectors of DDR1 are ill-defined (16, 17); however, we found that phosphorylation of PYK2 and PEAK1 was induced by collagen robustly in AsPc-1 cells but less so in PANC-1 and BxPC-3 cells.”
BackgroundDiscoidin domain receptor tyrosine kinases: new players in cancer progression
Valiathan, R. R., Marco, M., Leitinger, B., Kleer, C. G., & Fridman, R. A. (2012) · Cancer and Metastasis Reviews · doi:10.1007/s10555-012-9346-z · Cited by 384 · cited 3×
“The downstream effectors of DDR1 are ill-defined (16, 17); however, we found that phosphorylation of PYK2 and PEAK1 was induced by collagen robustly in AsPc-1 cells but less so in PANC-1 and BxPC-3 cells.”
BackgroundShintani, Y., Fukumoto, Y., Chaika, N. V., Svoboda, R. A., Wheelock, M. J., & Johnson, K. R. (2008) · The Journal of Cell Biology · doi:10.1083/jcb.200708137 · Cited by 284 · cited 4×
“DDR1 inhibition has also been shown to reduce tumorigenicity in multiple tumor models (23, 25, 51, 52).”
BackgroundInfluentialDay, E., Waters, B., Spiegel, K., Alnadaf, T., Manley, P. W., Buchdunger, E., Walker, C., & Járai, G. (2008) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2008.10.014 · Cited by 278 · cited 1×
“22 Several small molecule inhibitors (imatinib, nilotinib, and dasatinib) that target breakpoint cluster region-Abelson kinase (BCR-ABL) also potently inhibit DDR1/DDR2 activity (53,54).”
BackgroundSato, N., Fukushima, N., Maehara, N., Matsubayashi, H., Koopmann, J., Su, G. H., Hruban, R. H., & Goggins, M. (2003) · Oncogene · doi:10.1038/sj.onc.1206807 · Cited by 273 · cited 1×
“Furthermore, prior reports on the expression of SPARC in pancreatic tumor cells demonstrated that there is a reduction in SPARC expression by promoter hypermethylation in a high frequency of pancreatic tumor cells and other epithelial cancer cells (43, 44).”
BackgroundAlves, F., Vogel, W. F., Mossie, K. G., Millauer, B., Höfler, H., & Ullrich, A. (1995) · PubMed · Cited by 253
Why the stroma matters in breast cancer
Conklin, M. W., & Keely, P. J. (2012) · Cell Adhesion & Migration · doi:10.4161/cam.20567 · Cited by 241 · cited 1×
“Specifically, the amount of ECM deposition correlates with a poor prognosis in cancer patients and ECM-mediated signaling can promote tumor cell survival and invasion (1-4).”
BackgroundOngusaha, P. P., Kim, J., Fang, L., Wong, T. W., Yancopoulos, G. D., Aaronson, S. A., & Lee, S. W. (2003) · The EMBO Journal · doi:10.1093/emboj/cdg129 · Cited by 198 · cited 2×
“This is consistent with reports that collagen signaling is associated with chemoresistance in PDA cell lines (3, 48) and that DDR1 confers resistance to chemotherapy and mediates prosurvival signals (20, 21, 49).”
BackgroundJohnson, J. D., Edman, J. C., & Rutter, W. J. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.12.5677 · Cited by 182 · cited 1×
“DDR1 and DDR2 are differentially expressed amongst tissue and cell types: DDR1 expression is predominant in epithelial cells and is found at high levels in the pancreas, brain, lung, kidney, spleen, and placenta (8-11), while DDR2 is found in cells of connective tissues that originate from embryonic mesoderm and is ex…”
BackgroundAmbrogio, C., Goméz-López, G., Falcone, M., Vidal, A., Nadal, E., Crosetto, N., Blasco, R. B., Fernández-Marcos, P. J., Sánchez‐Céspedes, M., Ren, X., et al. (2016) · Nature Medicine · doi:10.1038/nm.4041 · Cited by 178 · cited 1×
“We establish here that activation of DDR1 contributes to the tumorigenic properties of PDA and that pharmacologically inhibiting this receptor tyrosine kinase with the selective DDR1 small molecule 7rh (28-31) slows tumor progression and enhances chemoresponse to standard-of-care PDA regimens.”
BackgroundSelf-citationGao, M., Duan, L., Luo, J., Zhang, L., Lu, X., Zhang, Y., Zhang, Z., Tu, Z., Xu, Y., Ren, X., et al. (2013) · Journal of Medicinal Chemistry · doi:10.1021/jm301824k · Cited by 168 · cited 3×
“In addition, we found that a novel small-molecule inhibitor, 7rh benzamide (28), effectively abrogated DDR1 signaling thereby reducing liquid colony tumor cell formation and tumor cell migration.”
BackgroundInfluentialSelf-citationValencia, K., Ormazabal, C., Zandueta, C., Luis-Ravelo, D., Antón, I., Pajares, M. J., Agorreta, J., Montuenga, L. M., Martínez-Canarias, S., Leitinger, B., et al. (2012) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-11-1686 · Cited by 149 · cited 2×
“DDR1 inhibition has also been shown to reduce tumorigenicity in multiple tumor models (23, 25, 51, 52).”
BackgroundFord, C. E., Lau, S. A., Zhu, C., Andersson, T., Tsao, M., & Vogel, W. F. (2007) · British Journal of Cancer · doi:10.1038/sj.bjc.6603614 · Cited by 142
A Dosage-Dependent Requirement for Sox9 in Pancreatic Endocrine Cell Formation
Seymour, P. A., Freude, K., Dubois, C. L., Shih, H., Patel, N., & Sander, M. (2008) · Developmental Biology · doi:10.1016/j.ydbio.2008.07.034 · Cited by 141 · cited 3×
“Sox9 is expressed in the malignant epithelium and is confined to the duct-like cells; differentiated acinar and endocrine cells do not express Sox9 (36, 37).”
BackgroundTai, I. T., Dai, M., Owen, D. A., & Chen, L. B. (2005) · Journal of Clinical Investigation · doi:10.1172/jci23002 · Cited by 140 · cited 1×
“In addition, it was reported that the restoration of SPARC expression enhanced radiosensitivity and chemosensitivity in preclinical models of colon cancer (45) and that SPARC expression enhanced chemoresponse in cancer patients (46, 47).”
BackgroundAlves, F., Saupe, S., Ledwon, M., Schaub, F., Hiddemann, W., & Vogel, W. F. (2001) · The FASEB Journal · doi:10.1096/fj.00-0626fje · Cited by 114 · cited 1×
“DDR1 and DDR2 are differentially expressed amongst tissue and cell types: DDR1 expression is predominant in epithelial cells and is found at high levels in the pancreas, brain, lung, kidney, spleen, and placenta (8-11), while DDR2 is found in cells of connective tissues that originate from embryonic mesoderm and is ex…”
BackgroundMapping of DDR1 Distribution and Oligomerization on the Cell Surface by FRET Microscopy
Mihai, C., Chotani, M. A., Elton, T. S., & Agarwal, G. (2008) · Journal of Molecular Biology · doi:10.1016/j.jmb.2008.10.067 · Cited by 112 · cited 1×
“Consistent with other reports (38), we found that activation of DDR1 resulted in decreased expression of total DDR1 (Fig.”
ResultCheetham, S., Tang, M., Mesak, F., Kennecke, H. F., Owen, D., & Tai, I. T. (2008) · British Journal of Cancer · doi:10.1038/sj.bjc.6604377 · Cited by 111 · cited 3×
“Primary tumors (44) and PATX samples (150) showed robust activation of DDR1 and PEAK1 (Fig.”
BackgroundDas, S., Ongusaha, P. P., Yang, Y. S., Park, J.-M., Aaronson, S. A., & Lee, S. W. (2006) · Cancer Research · doi:10.1158/0008-5472.can-06-1215 · Cited by 105 · cited 2×
“This is consistent with reports that collagen signaling is associated with chemoresistance in PDA cell lines (3, 48) and that DDR1 confers resistance to chemotherapy and mediates prosurvival signals (20, 21, 49).”
BackgroundAguilera, K. Y., Rivera, L. B., Hur, H., Carbon, J. G., Toombs, J. E., Goldstein, C. D., Dellinger, M. T., Castrillon, D. H., & Brekken, R. A. (2014) · Cancer Research · doi:10.1158/0008-5472.can-13-2800 · Cited by 100 · cited 1×
“We previously found that the matricellular protein Sparc (secreted protein acidic and rich in cysteine) reduced collagen I signaling through Ddr1 and that loss of Sparc accelerated PDA progression with a concordant increase in Ddr1 signaling (42).”
BackgroundSelf-citationLindner, J., Loibl, S., Denkert, C., Ataseven, B., Fasching, P. A., Pfitzner, B. M., Gerber, B., Gade, S., Darb‐Esfahani, S., Sinn, B. V., et al. (2014) · Annals of Oncology · doi:10.1093/annonc/mdu487 · Cited by 98 · cited 1×
“In addition, it was reported that the restoration of SPARC expression enhanced radiosensitivity and chemosensitivity in preclinical models of colon cancer (45) and that SPARC expression enhanced chemoresponse in cancer patients (46, 47).”
BackgroundCader, F. Z., Vockerodt, M., Bose, S., Nagy, E., Bründler, M., Kearns, P. R., & Murray, P. G. (2013) · Blood · doi:10.1182/blood-2013-04-499004 · Cited by 93 · cited 2×
“This is consistent with reports that collagen signaling is associated with chemoresistance in PDA cell lines (3, 48) and that DDR1 confers resistance to chemotherapy and mediates prosurvival signals (20, 21, 49).”
BackgroundMiao, L., Zhu, S., Wang, Y., Li, Y., Ding, J., Dai, J., Cai, H., Zhang, D., & Song, Y. (2013) · Medical Oncology · doi:10.1007/s12032-013-0626-4 · Cited by 86
Kerroch, M., Guerrot, D., Vandermeersch, S., Placier, S., Mesnard, L., Jouanneau, C., Rondeau, É., Ronco, P. M., Boffa, J., Chatziantoniou, C., et al. (2012) · The FASEB Journal · doi:10.1096/fj.11-194902 · Cited by 78 · cited 1×
“DDR1 is upregulated in fibrotic diseases and contributes to the initiation and progression of fibrosis (50).”
BackgroundCouvelard, A., Hu, J., Steers, G., O’Toole, D., Sauvanet, A., Belghiti, J., Bédossa, P., Gatter, K. C., Ruszniewski, P. B., & Pezzella, F. (2006) · Gastroenterology · doi:10.1053/j.gastro.2006.09.007 · Cited by 75 · cited 1×
“DDR1 and DDR2 are differentially expressed amongst tissue and cell types: DDR1 expression is predominant in epithelial cells and is found at high levels in the pancreas, brain, lung, kidney, spleen, and placenta (8-11), while DDR2 is found in cells of connective tissues that originate from embryonic mesoderm and is ex…”
BackgroundBeck, A. W., Luster, T. A., Miller, A. F., Holloway, S. E., Conner, C. R., Barnett, C. C., Thorpe, P. E., Fleming, J. B., & Brekken, R. A. (2005) · International Journal of Cancer · doi:10.1002/ijc.21684 · Cited by 74 · cited 2×
“Pan02 cells (5 10(5)) were injected orthotopically in 6- to 8-week-old C57BL/6 mice as described previously (33, 34).”
MethodSelf-citationPark, H., Kim, K. M., Lee, H. C., Choi, H. N., Kim, D. J., Kim, B., & Moon, W. (2007) · Oncology Reports · doi:10.3892/or.18.6.1435 · Cited by 74
Small Molecule Discoidin Domain Receptor Kinase Inhibitors and Potential Medical Applications
Li, Y., Lu, X., Ren, X., & Ding, K. (2015) · Journal of Medicinal Chemistry · doi:10.1021/jm5012319 · Cited by 72 · cited 1×
“DDR1 inhibition has also been shown to reduce tumorigenicity in multiple tumor models (23, 25, 51, 52).”
BackgroundSelf-citationKarn, T., Holtrich, U., Bräuninger, A., Böhme, B., Wolf, G., Rübsamen‐Waigmann, H., & Strebhardt, K. (1993) · PubMed · Cited by 72
Laval, S. H., Butler, R. J., Shelling, A. N., Hanby, A. M., Poulsom, R., & Ganesan, T. S. (1994) · PubMed · Cited by 71
Huang, H., Svoboda, R. A., Lazenby, A. J., Saowapa, J., Chaika, N. V., Ding, K., Wheelock, M. J., & Johnson, K. R. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.m116.740605 · Cited by 71 · cited 2×
“At pharmacologically-relevant concentrations, 7rh inhibited activation of PYK2 and PEAK1, signaling proteins downstream of DDR1 (40).”
BackgroundSelf-citationArnold, S. A., Mira, E., Muneer, S., Korpanty, G. J., Beck, A. W., Holloway, S. E., Mañes, S., & Brekken, R. A. (2008) · Experimental Biology and Medicine · doi:10.3181/0801-rm-12 · Cited by 70 · cited 2×
“Pan02 cells (5 10(5)) were injected orthotopically in 6- to 8-week-old C57BL/6 mice as described previously (33, 34).”
MethodSelf-citationDiscoidin domain receptor 1 activity drives an aggressive phenotype in gastric carcinoma
Hur, H., Ham, I., Lee, D., Jin, H., Aguilera, K. Y., Oh, H. J., Han, S., Kwon, J. E., Kim, Y.-B., Ding, K., et al. (2017) · BMC Cancer · doi:10.1186/s12885-017-3051-9 · Cited by 68 · cited 1×
“In addition, we have recently reported that DDR1 expression and activity correlates with worse outcome in a cohort of gastric cancer patients (31).”
BackgroundSelf-citationStructure and expression of the Tyro 10 receptor tyrosine kinase.
Lai, C. K., & Lemke, G. (1994) · PubMed · Cited by 64
Targeting the Cancer-Stroma Interaction: A Potential Approach for Pancreatic Cancer Treatment
Li, X., Ma, Q., Xu, Q., Duan, W., Lei, J., & Wu, E. (2012) · Current Pharmaceutical Design · doi:10.2174/13816128112092404 · Cited by 62 · cited 1×
“This fibrotic network contributes to the development of a complex tumor microenvironment that promotes PDA development, invasion, metastasis, and resistance to chemotherapy (41).”
BackgroundPitini, V. V., Arrigo, C., Mirto, C. D., Mondello, P., & Altavilla, G. (2013) · Lung Cancer · doi:10.1016/j.lungcan.2013.07.004 · Cited by 58 · cited 1×
“Dasatinib in particular has demonstrated promising therapeutic efficacy in lung cancer cells (57) and squamous cell carcinoma patients (58) harboring gain-of-function DDR2 mutations.”
BackgroundTherapeutic Potential of Perineural Invasion, Hypoxia and Desmoplasia in Pancreatic Cancer
Liu, H., Ma, Q., Xu, Q., Lei, J., Li, X., Wang, Z., & Wu, E. (2012) · Current Pharmaceutical Design · doi:10.2174/13816128112092395 · Cited by 51 · cited 1×
“Scoring system is denoted as: low or no reactivity (0–1), moderate reactivity (2), strong reactivity (3), and very strong reactivity (4).”
BackgroundSelf-citationPerez, J. L., Shen, X., Finkernagel, S. W., Sciorra, L. J., Jenkins, N. A., Gilbert, D. J., Copeland, N. G., & Wong, T. W. (1994) · PubMed · Cited by 47
Fibulin-5 blocks microenvironmental ROS in pancreatic cancer
Wang, M., Topalovski, M., Toombs, J. E., Wright, C. M., Moore, Z. R., Boothman, D., Yanagisawa, H., Wang, H.-M., Witkiewicz, A., Castrillon, D., et al. (2015) · Cancer Research · doi:10.1158/0008-5472.can-15-0744 · Cited by 41 · cited 1×
“(KPC) mice were generated as described previously (32).”
MethodSelf-citationJian, Z., Sun, J., Chen, W., Jin, H., Zheng, J.-H., & Wu, Y.-L. L. C. (2012) · Medical Oncology · doi:10.1007/s12032-012-0277-x · Cited by 22
Maass, N., Schem, C., Bauerschlag, D., Tiemann, K., Schaefer, F. W., Hanson, S., Muth, M., Baier, M. L., Weigel, M. T., Wenners, A. S., et al. (2014) · Oncology · doi:10.1159/000365553 · Cited by 19 · cited 1×
“Thus, the potential activity of imatinib and vinorelbine in a phase I/II trial in metastatic breast cancer patients (55), as well as dasatinib in numerous clinical trials in solid tumors (56), could be due in part to the inhibition of DDRs.”
BackgroundAnticancer Effects of Mesothelin-Targeted Immunotoxin Therapy Are Regulated by Tyrosine Kinase DDR1
Ali-Rahmani, F. G., FitzGerald, D. J., Martin, S. E., Patel, P., Prunotto, M., Ormanoglu, P., Thomas, C. J., & Pastan, I. H. (2016) · Cancer Research · doi:10.1158/0008-5472.can-15-2401 · Cited by 18 · cited 1×
“We establish here that activation of DDR1 contributes to the tumorigenic properties of PDA and that pharmacologically inhibiting this receptor tyrosine kinase with the selective DDR1 small molecule 7rh (28-31) slows tumor progression and enhances chemoresponse to standard-of-care PDA regimens.”
BackgroundBrooks, E. G., Connors, J. M., Sehn, L. H., Gascoyne, R. D., Savage, K. J. J., Shenkier, T. N., Klasa, R. J., Gerrie, A. S., Skinnider, B., Slack, G. W., et al. (2013) · Blood · doi:10.1182/blood.v122.21.4237.4237 · Cited by 7
Cited by
Sorted by citations
Pancreatic cancer: Advances and challenges
Halbrook, C. J., Lyssiotis, C. A., Pasca di Magliano, M., & Maitra, A. (2023) · Cell · doi:10.1016/j.cell.2023.02.014 · Cited by 1,321
Yuan, Z., Li, Y., Zhang, S., Wang, X., Dou, H., Yu, X., Zhang, Z., Yang, S., & Xiao, M. (2023) · Molecular Cancer · doi:10.1186/s12943-023-01744-8 · Cited by 977
“These results depict a distinguish role of collagen in PDAC compared to other cancers.”
BackgroundInfluentialExtracellular matrix and its therapeutic potential for cancer treatment
Huang, J., Zhang, L., Wan, D., Zhou, L., Zheng, S., Lin, S., & Qiao, Y. (2021) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-021-00544-0 · Cited by 962
“Aguilera et al.(500) knocked down DDR1 by siRNA and found that migration was inhibited in pancreatic ductal adenocarcinoma cells.”
BackgroundPancreatic cancer stroma: an update on therapeutic targeting strategies
Hosein, A. N., Brekken, R. A., & Maitra, A. (2020) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-020-0300-1 · Cited by 950
Self-citationThe role of collagen in cancer: from bench to bedside
Xu, S., Xu, H., Wang, W., Li, S., Li, H., Li, T., Zhang, W., Yu, X., & Liu, L. (2019) · Journal of Translational Medicine · doi:10.1186/s12967-019-2058-1 · Cited by 735
Metadata
- Authors
- Aguilera, K. Y., Huang, H., Du, W., Hagopian, M. M., Wang, Z., Hinz, S., Hwang, T. H., Wang, H., Fleming, J. B., Castrillon, D. H., Ren, X., Ding, K., & Brekken, R. A.
- Affiliations
- The University of Texas Southwestern Medical Center (US)
- Jinan University (CN)
- The University of Texas MD Anderson Cancer Center (US)
- 6Department of Clinical Science, UT Southwestern Medical Center, Dallas, Texas.
- Corresponding author
- Brekken, Rolf A.
- ORCID
- Venue
- Molecular Cancer Therapeutics
- Published
- 2017-11-01
- Volume
- 16
- Issue
- 11
- Pages
- 2473-2485
- ISSN
- 1535-7163 (ISSN-L)
- 1538-8514
- PMC
- PMC5669827
- OpenAlex
- W2751614779
- Cited by
- 118
- References
- 61
- Citations by year
- 2026: 6 · 2025: 12 · 2024: 17 · 2023: 12 · 2022: 15 · 2021: 16 · 2020: 15 · 2019: 15 · 2018: 9 · 2017: 1
- FWCI
- 4.82
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Molecular Cancer Therapeutics (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NIH (R01CA118240, U54 CA210181, F31 CA168350)
- CPRIT (RP160211)
- National Science Fund (#81425021)
- Guangdong province (#2016A050502041)
- Topics
- Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Keywords
- DDR1, pancreatic ductal adenocarcinoma, collagen signaling, extracellular matrix, Pyk2, PEAK1, kinase inhibitors, chemosensitization, tumor cell migration, tumor cell proliferation, combination chemotherapy
- MeSH terms
- Discoidin Domain Receptor 1, Adenocarcinoma, Animals, Cell Adhesion, Cell Movement, Collagen, Humans, Protein-Tyrosine Kinases, Signal Transduction, Carcinoma, Pancreatic Ductal, Xenograft Model Antitumor Assays, Cell Proliferation, Mice, Focal Adhesion Kinase 1, Small Molecule Libraries, Carcinogenesis
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 ›
Are you an author, or do you see a problem with this page? Request a review
