The DOI matches its Crossref record; 104 of the 104 references it cites were found in a registry or an index.
Modes of resistance to anti-angiogenic therapy
Open accessAbstract
Angiogenesis inhibitors targeting the vascular endothelial growth factor (VEGF) signalling pathways are affording demonstrable therapeutic efficacy in mouse models of cancer and in an increasing number of human cancers. However, in both preclinical and clinical settings, the benefits are at best transitory and are followed by a restoration of tumour growth and progression. Emerging data support a proposition that two modes of unconventional resistance underlie such results: evasive resistance, an adaptation to circumvent the specific angiogenic blockade; and intrinsic or pre-existing indifference. Multiple mechanisms can be invoked in different tumour contexts to manifest both evasive and intrinsic resistance, motivating assessment of their prevalence and importance and in turn the design of pharmacological strategies that confer enduring anti-angiogenic therapies.
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
“Drug resistance in cancer can be cell-intrinsic (Poulikakos and Rosen, 2011) or a combination of host and tumor mediated pathways (Bergers and Hanahan, 2008; Ebos et al., 2009).”
From A CXCL1 Paracrine Network Links Cancer Chemoresistance and Metastasis (2012) · cites this paper as Bergers and Hanahan, 2008
In the citing paper
“Several cellular and molecular mechanisms of escape from antiangiogenic therapies have been postulated and investigated, including activation of alternative angiogenic pathways, recruitment of proangiogenic myeloid cells, increased pericyte cell coverage of tumour blood vessels, increased tumour cell invasion, and alternative modes of vessel recruitment7,9,80”
From Enhancing cancer immunotherapy using antiangiogenics: opportunities and challenges (2018) · cites this paper as [80]
In the citing paper
“This dual blockade approach can provide tumour control in some preclinical models, although the degree of benefit and the underlying mechanism of action seem to be context-dependent31,32,80,89.”
From Enhancing cancer immunotherapy using antiangiogenics: opportunities and challenges (2018) · cites this paper as [80]
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
Hanahan, D., & Weinberg, R. A. (2000) · Cell · doi:10.1016/s0092-8674(00)81683-9 · Cited by 29,219
Self-citationIsolation of Putative Progenitor Endothelial Cells for Angiogenesis
Asahara, T., Murohara, T., Sullivan, A., Silver, M., van der Zee, R., Li, T., Witzenbichler, B., Schatteman, G., & Isner, J. M. (1997) · Science · doi:10.1126/science.275.5302.964 · Cited by 8,725 · cited 1×
“Endothelial and pericyte progenitors differentiate into endothelial cells, which form the inner lining of blood vessel walls, or pericytes, the cells that envelop blood vessels, respectivel”
BackgroundPatterns and emerging mechanisms of the angiogenic switch during tumorigenesis
Hanahan, D., & Folkman, J. (1996) · Cell · doi:10.1016/s0092-8674(00)80108-7 · Cited by 6,885
Self-citationTargeting HIF-1 for cancer therapy
Semenza, G. L. (2003) · Nature Reviews Cancer · doi:10.1038/nrc1187 · Cited by 6,717 · cited 1×
“The HIF regulatory network also holds promise as a target, given its global effects on angiogenesis, invasion and stress-adaptive cell physiolog”
BackgroundNormalization of Tumor Vasculature: An Emerging Concept in Antiangiogenic Therapy
Jain, R. K. (2005) · Science · doi:10.1126/science.1104819 · Cited by 5,527
Angiogenesis in life, disease and medicine
Carmeliet, P. (2005) · Nature · doi:10.1038/nature04478 · Cited by 3,551
Tumour-educated macrophages promote tumour progression and metastasis
Pollard, J. W. (2004) · Nature reviews. Cancer · doi:10.1038/nrc1256 · Cited by 3,413 · cited 1×
“By contrast, pro-angiogenic monocytes, such as tumour-associated macrophage”
BackgroundVEGFR1-positive haematopoietic bone marrow progenitors initiate the pre-metastatic niche
Kaplan, R. N., Riba, R. D., Zacharoulis, S., Bramley, A. H., Vincent, L., Costa, C., MacDonald, D. D., Jin, D. K., Shido, K., Kerns, S. A., et al. (2005) · Nature · doi:10.1038/nature04186 · Cited by 3,288
Paclitaxel plus Bevacizumab versus Paclitaxel Alone for Metastatic Breast Cancer
Miller, K. D., Wang, M., Gralow, J. R., Dickler, M. N., Cobleigh, M., Perez, E. A., Shenkier, T. N., Cella, D. F., & Davidson, N. E. (2007) · New England Journal of Medicine · doi:10.1056/nejmoa072113 · Cited by 3,104 · cited 1×
“aspx?CdrID=39762">paclitaxel extended progression-free survival (but not overall survival”
BackgroundProgenitor cell trafficking is regulated by hypoxic gradients through HIF-1 induction of SDF-1
Ceradini, D. J., Kulkarni, A. R., Callaghan, M. J., Tepper, O. M., Bastidas, N., Kleinman, M. E., Capla, J. M., Galiano, R. D., Levine, J. P., & Gurtner, G. C. (2004) · Nature Medicine · doi:10.1038/nm1075 · Cited by 2,600 · cited 1×
“Evidence that low oxygen tension triggers the recruitment of BMDCs stems from observations in experimentally induced ischaemic tissue, wherein endothelial progenitors and other CXCR4 + BMDCs are recruited, in part through increases in HIF1α and its downstream effectors SDF1α (a CXCR4 ligand) and VEGF itsel”
Background
Flagged first, then by citations
Research works printed but not linked: 1
- Berger, M. S. & Wilson, C. B. The Gliomas (W.B. Saunders, Philadelphia, 1999).
Cited by
Sorted by citations
Items 401–500 of 1,005
Response Assessment in Neuro-Oncology
Lee, E. Q., & Wen, P. Y. (2010) · Current Oncology Reports · doi:10.1007/s11912-010-0143-y · Cited by 110
The vasohibin family: a novel family for angiogenesis regulation
Sato, Y. (2012) · The Journal of Biochemistry · doi:10.1093/jb/mvs128 · Cited by 113
“Another problem is drug resistance due to the switch from VEGF to other angiogenic stimulators (44).”
BackgroundFunctional subsets of mesenchymal cell types in the tumor microenvironment
Cortez, E., Roswall, P., & Pietras, K. (2014) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2013.12.010 · Cited by 112
“Together, these results support the premise that PC promote resistance to anti-VEGF therapy [69], and that expression of α-SMA denotes a phenotype of PC from adjacent non-malignant tissues.”
ResultEndothelial cell metabolism: parallels and divergences with cancer cell metabolism
Verdegem, D., Moens, S., Stapor, P. C., & Carmeliet, P. (2014) · Cancer & Metabolism · doi:10.1186/2049-3002-2-19 · Cited by 117
“Indeed, tumors can rely on other pro-angiogenic factors besides VEGF or on angiogenic molecules produced by associated stromal cells, making the treatment ineffective [2-5].”
BackgroundSitravatinib potentiates immune checkpoint blockade in refractory cancer models
Du, W., Huang, H., Sorrelle, N. B., & Brekken, R. A. (2018) · JCI Insight · doi:10.1172/jci.insight.124184 · Cited by 110
Joosten, S. C., Hamming, L. C., Soetekouw, P. M. M. B., Aarts, M. J. B., Veeck, J., van Engeland, M., & Tjan‐Heijnen, V. C. G. (2014) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2014.11.002 · Cited by 113
“endothelial and pericyte progenitors) and vascularmodulatory cells [77], including tumor-associated macrophages (TAMs) [78], Tie2+ monocytes [79], VEGFR1+ hemangiocytes [80,81] and CD11b + myeloid cells [82].”
BackgroundTargeting HIF-2 α in clear cell renal cell carcinoma: A promising therapeutic strategy
Martínez‐Sáez, O., Borau, P. G., Alonso‐Gordoa, T., Molina‐Cerrillo, J., & Grande, E. (2017) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2017.01.013 · Cited by 111
“…s ( l H 2 2 s a C t 2 Y p c e e m n i T H O. Martínez-Sáez et al. / Critical Reviews esistance of RCC. Clinical data support activity of several comounds in resistant patient populations (Rini and Atkins, 2009; uang et al., 2009; Bhatt et al., 2010; Bergers and Hanahan, 2008; ennino et al., 2012).”
BackgroundHe, B., Jabouille, A., Steri, V., Johansson, A., Michael, I. P., Kotamraju, V. R., Junckerstorff, R. C., Nowak, A. K., Hamzah, J., Lee, G., et al. (2018) · The Journal of Pathology · doi:10.1002/path.5080 · Cited by 110
Self-citationPeptide-Based Agents for Cancer Treatment: Current Applications and Future Directions
Nhàn, N. T. T., Yamada, T., & Yamada, K. H. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241612931 · Cited by 114
“However, resistance to VEGF inhibitors occurs through various mechanisms [143].”
BackgroundSmall GTPase R-Ras Regulates Integrity and Functionality of Tumor Blood Vessels
Sawada, J., Urakami, T., Li, F., Urakami, A., Zhu, W., Fukuda, M., Li, D. Y., Ruoslahti, E. I., & Komatsu, M. (2012) · Cancer Cell · doi:10.1016/j.ccr.2012.06.013 · Cited by 110
“This study revealed a key role for R-Ras in promoting tum role, R-Ras expressed in endothelial cells and in pericytes bot suggests R-Ras as a potential target for controlling blood circ cally impacts tumor progression and tumors responses to therapeutic regimens (Bergers and Hanahan, 2008; Carmeliet and Jain, 2011b).”
Tumor angiogenesis, from foe to friend
Rivera, L. B., & Bergers, G. (2015) · Science · doi:10.1126/science.aad0862 · Cited by 112
Self-citationHu, W., Lu, C., Dong, H. H., Huang, J., Shen, D.-Y., Stone, R. L., Nick, A. M., Shahzad, M. M. K., Mora, E., Jennings, N. B., et al. (2011) · Cancer Research · doi:10.1158/0008-5472.can-10-2719 · Cited by 108
“The tumor vasculature is complex and the process of angiogenesis in cancers relies on many factors that are not fully understood (21, 22).”
BackgroundThe emerging roles of macrophages in cancer metastasis and response to chemotherapy
Sanchez, L. R., Borriello, L., Entenberg, D. R., Condeelis, J. S., Oktay, M. H., & Karagiannis, G. S. (2019) · Journal of Leukocyte Biology · doi:10.1002/jlb.mr0218-056rr · Cited by 106
VEGF/Neuropilin Signaling in Cancer Stem Cells
Mercurio, A. M. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20030490 · Cited by 108
“This observation may explain, in part, the dismal efficacy of bevacizumab for many cancers [72,73], and it reinforces the potential benefit of targeting the NRPs directly as an approach to inhibiting VEGF signaling in CSCs.”
BackgroundAntiangiogenic Activity of 2-Deoxy-D-Glucose
Merchan, J. R., Kovács, K., Railsback, J. W., Kurtoğlu, M., Jing, Y., Piña, Y., Gao, N., Murray, T. G., Lehrman, M. A., & Lampidis, T. J. (2010) · PLoS ONE · doi:10.1371/journal.pone.0013699 · Cited by 111
“anti-VEGF) antiangiogenic agents [44].”
Sorrentino, C., Miele, L., Porta, A., Pinto, A., & Morello, S. (2015) · Oncotarget · doi:10.18632/oncotarget.4393 · Cited by 112
“Accumulation of Gr1+ myeloid cells in the tumor microenvironment increases tumor angiogenesis [18, 20] and mediates tumors refractoriness to anti-VEGF treatment [45, 46].”
Role of miR-132 in Angiogenesis after Ocular Infection with Herpes Simplex Virus
Mulik, S., Xu, J. J., Reddy, P. B. J., Rajasagi, N. K., Giménez, F., Sharma, S., Lu, P. Y., & Rouse, B. T. (2012) · American Journal Of Pathology · doi:10.1016/j.ajpath.2012.04.014 · Cited by 108
“Thus, antiangiogenic therapies that target single pathways, such as VEGFR signaling, often develop resistance by upregulating alternative angiogenic growth factors.(33) This problem can be avoided using miR-132 because it removes an endogenous regulator (Ras-GAP) involved in controlling responses to several angiogenic…”
BackgroundVasculogenesis: a crucial player in the resistance of solid tumours to radiotherapy
Brown, J. M. (2013) · British Journal of Radiology · doi:10.1259/bjr.20130686 · Cited by 107
Angiogenesis and expression of PDGF ‐ C , VEGF , CD 105 and HIF ‐1α in human glioblastoma
Clara, C., Marie, S. K. N., Almeida, J. R. W., Wakamatsu, A., Oba‐Shinjo, S. M., Uno, M., Neville, M. A., & Rosemberg, S. (2014) · Neuropathology · doi:10.1111/neup.12111 · Cited by 106
Targeting VEGF pathway to normalize the vasculature: an emerging insight in cancer therapy
Wu, J., Tang, Y., & Liang, X. (2018) · OncoTargets and Therapy · doi:10.2147/ott.s172042 · Cited by 113
“Moreover, it leads to radioresistance and chemoresistance, even metastasis and relapse.(12) To overcome the disadvantages of anti-angiogenesis, Jain proposed a novel concept aimed at tumor angiogenesis, which was named “vascular normalization.”
BackgroundState of the art and future directions of pancreatic ductal adenocarcinoma therapy
Neuzillet, C., Tijeras‐Raballand, A., Bourget, P., Cros, J. F., Couvelard, A., Sauvanet, A., Vullierme, M., Tournigand, C., & Hammel, P. R. (2015) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2015.08.006 · Cited by 114
Calleri, A., Bono, A., Bagnardi, V., Quarna, J., Mancuso, P., Rabascio, C., Dellapasqua, S., Campagnoli, E., Shaked, Y., Goldhirsch, A., et al. (2009) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-09-1493 · Cited by 106
The Role of Hypoxia and Cancer Stem Cells in Renal Cell Carcinoma Pathogenesis
Myszczyszyn, A., Czarnecka, A. M., Matak, D., Szymański, Ł., Lian, F., Kornakiewicz, A., Bartnik, E., Kukwa, W., Kiéda, C., & Szczylik, C. A. (2015) · Stem Cell Reviews and Reports · doi:10.1007/s12015-015-9611-y · Cited by 109
Role of endothelial progenitor cells in cancer progression
Moschetta, M., Mishima, Y., Şahin, İ., Manier, S., Glavey, S. V., Vacca, A., Roccaro, A. M., & Ghobrial, I. M. (2014) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2014.03.005 · Cited by 109
“Like VDAs, high dose antiangiogenic drugs can cause vessel regression, an acute increase in intratumoral hypoxia, and in some cases, in activation of HIF-1 alpha in tumor cells [118].”
BackgroundControlling angiogenesis in breast cancer: A systematic review of anti-angiogenic trials
Mackey, J. R., Kerbel, R. S., Gelmon, K. A., McLeod, D., Chia, S., Rayson, D., Verma, S., Collins, L. L., Paterson, A. H. G., Robidoux, A., et al. (2012) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2011.12.002 · Cited by 104
Role of placenta growth factor in cancer and inflammation
Kim, K.-J., Cho, C., & Kim, W. (2011) · Experimental & Molecular Medicine · doi:10.3858/emm.2012.44.1.023 · Cited by 105
“However, a substantial fraction of tumors are resistant to current anti-angiogenic therapies and relapses are not even uncommon after a progression-free period (Hurwitz et al., 2004; Bergers and Hanahan, 2008; Burris and Rocha-Lima, 2008).”
BackgroundEisen, 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
Pak, R. W., Hadjiabadi, D. H., Senarathna, J., Agarwal, S., Thakor, N. V., Pillai, J. J., & Pathak, A. P. (2017) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x17707398 · Cited by 109
“Furthermore, activation of alternative angiogenic pathways, hypoxia-induced increases in angiogenic signaling molecules, and recruitment of stem cells also result in resistance to anti-angiogenic therapy.(101,102) Therefore, there is an exigent need to identify more specific and sensitive fMRI-based biomarkers that ca…”
BackgroundThe role of interleukin‑6‑STAT3 signalling in glioblastoma (Review)
West, A. J., Tsui, V., Stylli, S. S., Nguyen, H. P. T., Morokoff, A. P., Kaye, A. H., & Luwor, R. B. (2018) · Oncology Letters · doi:10.3892/ol.2018.9227 · Cited by 104
“It has been observed that high expression of VEGF correlates with higher tumour grade and shorter survival (57,58), while one of the mechanisms of progression in glioblastoma is postulated to involve tumour resistance to anti-angiogenic treatments (59,60).”
BackgroundSchmidt, T., & Carmeliet, P. (2010) · Nature · doi:10.1038/465697a · Cited by 105
Exploring Novel Methods for Modulating Tumor Blood Vessels in Cancer Treatment
Wong, P., Bodrug, N., & Hodivala‐Dilke, K. (2016) · Current Biology · doi:10.1016/j.cub.2016.09.043 · Cited by 104
Sox17 promotes tumor angiogenesis and destabilizes tumor vessels in mice
Yang, H., Lee, S., Lee, S., Kim, K., Yang, Y., Kim, J. H., Adams, R. H., Wells, J. M., Morrison, S. J., Koh, G. Y., et al. (2012) · Journal of Clinical Investigation · doi:10.1172/jci64547 · Cited by 103
“Despite therapeutic success for some cancers, blockade of these pathways occasionally results in incomplete inhibition or evasive activation of tumor angiogenesis (6–9), emphasizing the need for a more complete understanding of angiogenic regulation.”
Advances in Chemotherapy of Differentiated Epithelial and Medullary Thyroid Cancers
Sherman, S. I. (2009) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2008-0923 · Cited by 104
Role of angiogenesis in the pathogenesis of cancer
Hoff, P. M., & Machado, K. K. (2012) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2012.04.006 · Cited by 105
Thrombospondin-1 Triggers Cell Migration and Development of Advanced Prostate Tumors
Firlej, V., Mathieu, J. R. R., Gilbert, C., Lemonnier, L., Nakhlé, J., Gallou‐Kabani, C., Guarmit, B., Morin, A., Prevarskaya, N. B., Delongchamps, N. B., et al. (2011) · Cancer Research · doi:10.1158/0008-5472.can-11-0833 · Cited by 103
Wang, Q., Gao, J., Di, W. J., & Wu, X. (2020) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-020-02576-x · Cited by 104
Therapeutic Targeting of Tumor Growth and Angiogenesis with a Novel Anti-S100A4 Monoclonal Antibody
Hernández, J. L., Padilla, L., Plaza, S. D., Coll, T., Hervas, R., Adán, J., Masa, M., Mitjans, F., Martinez, J. M., Coma, S., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0072480 · Cited by 101
“According to clinical data these therapies have not produced enduring efficacy in tumor reduction or long-term survival, due to an emergent resistance to the antiangiogenic therapy [6,7].”
BackgroundCyclin-dependent Kinase 5 Regulates Endothelial Cell Migration and Angiogenesis
Liebl, J., Weitensteiner, S. B., Vereb, G., Takács, L., Fürst, R., Vollmar, A. M., & Stefan Zahler, A. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.126177 · Cited by 103
Goedegebuure, P. S., Mitchem, J. B., Porembka, M. R., Tan, M. C. B., Belt, B. A., Wang‐Gillam, A., Gillanders, W. E., Hawkins, W. G., & Linehan, D. C. (2011) · Current Cancer Drug Targets · doi:10.2174/156800911796191024 · Cited by 104
“Acknowledgments Supported in part by NIH T32 CA09621 (JBM, MRP, MCBT) Abbreviations used MDSC myeloid-derived suppressor cell Treg T regulatory cell CTL cytotoxic T lymphocyte Th T helper IFN interferon MHC major histocompatibility complex PD-L1 programmed cell death ligand-1 TGFβ transforming growth factor beta IL in…”
BackgroundInfluentialMetronomic chemotherapy for cancer treatment: a decade of clinical studies
Romiti, A., Cox, M. C., Sarcina, I., Rocco, R. D., D’Antonio, C., Barucca, V., & Marchetti, P. (2013) · Cancer Chemotherapy and Pharmacology · doi:10.1007/s00280-013-2125-x · Cited by 103
Antiangiogenic Therapies: Going beyond Their Limits
Moserle, L., Jiménez-Valerio, G., & Casanovas, O. (2013) · Cancer Discovery · doi:10.1158/2159-8290.cd-13-0199 · Cited by 105
Okubo, M., Kioi, M., Nakashima, H., Sugiura, K., Mitsudo, K., Aoki, I., Taniguchi, H., & Tohnai, I. (2016) · Scientific Reports · doi:10.1038/srep27548 · Cited by 109
Resistance to Targeted Therapies in Renal Cancer: The Importance of Changing the Mechanism of Action
Durán, I., Lambea, J., Maroto, P., González-Larriba, J. L., Flores, L. E., Granados-Principal, S. M., Graupera, M., Sáez, B., Vivancos, A. P., & Casanovas, O. (2016) · Targeted Oncology · doi:10.1007/s11523-016-0463-4 · Cited by 101
MET: roles in epithelial-mesenchymal transition and cancer stemness
Jeon, H.-M., & Lee, J. (2017) · Annals of Translational Medicine · doi:10.21037/atm.2016.12.67 · Cited by 101
Fan, F., Samuel, S., Gaur, P., Lu, J., Dallas, N. A., Xia, L., Bose, D., Ramachandran, V., & Ellis, L. M. (2011) · British Journal of Cancer · doi:10.1038/bjc.2011.81 · Cited by 104
“Preclinical studies and clinical observations have now begun to shed light on the mechanisms of action of anti-VEGF therapy and acquired resistance (reviewed in Bergers and Hanahan (2008) and Ellis and Hicklin (2008, 2009)). Owing to the role of VEGF in mediating multiple components of the tumour microenvironment, mec…”
BackgroundMechanisms of resistance to vascular endothelial growth factor blockade
Abdullah, S. E., & Perez-Soler, R. (2011) · Cancer · doi:10.1002/cncr.26540 · Cited by 104
Effects of Sorafenib Dose on Acquired Reversible Resistance and Toxicity in Hepatocellular Carcinoma
Kuczynski, E. A., Lee, C. R., Man, S., Chen, E. X., & Kerbel, R. S. (2015) · Cancer Research · doi:10.1158/0008-5472.can-14-3687 · Cited by 99
Angiogenesis in cancer: Anti-VEGF escape mechanisms.
Prager, G. W., Poettler, M., Unseld, M., & Zielinski, C. C. (2012) · Europe PMC (PubMed Central) · doi:10.3978/j.issn.2218-6751.2011.11.02 · Cited by 101
“org protein expression of secondary molecules in order to sustain the neo-vascularization response (12), whereby in particular components of the EGFR and FGFR pathways were shown to be upregulated in the tumor stroma (13).”
BackgroundTamburrino, A., Piro, G., Carbone, C., Tortora, G., & Melisi, D. (2013) · Frontiers in Pharmacology · doi:10.3389/fphar.2013.00056 · Cited by 102
Tumor refractoriness to anti-VEGF therapy
Ribatti, D. (2016) · Oncotarget · doi:10.18632/oncotarget.8694 · Cited by 105
Recent Advancements of Nanomedicine towards Antiangiogenic Therapy in Cancer
Mukherjee, A., Madamsetty, V. S., Paul, M. K., & Mukherjee, S. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21020455 · Cited by 101
Type II Kinase Inhibitors: An Opportunity in Cancer for Rational Design
Blanc, J., Geney, R., & Menet, C. J. (2013) · Anti-Cancer Agents in Medicinal Chemistry · doi:10.2174/1871520611313050008 · Cited by 105
“Indeed, adaptive responses by the tumour and the vasculature to anti-VEGF therapy have been postulated [47].”
BackgroundAtu027 Prevents Pulmonary Metastasis in Experimental and Spontaneous Mouse Metastasis Models
Santel, A., Aleku, M., Röder, N., Möpert, K., Durieux, B., Janke, O., Keil, O., Endruschat, J., Dames, S., Lange, C. M., et al. (2010) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-10-1994 · Cited by 107
Endothelial Interleukin-6 Defines the Tumorigenic Potential of Primary Human Cancer Stem Cells
Krishnamurthy, S., Warner, K. A., Dong, Z., Imai, A., Nör, C., Ward, B. B., Helman, J. I., Taichman, R. S., Bellile, E. L., McCauley, L. K., et al. (2014) · Stem Cells · doi:10.1002/stem.1793 · Cited by 102
Anti-angiogenic treatment promotes triple-negative breast cancer invasion via vasculogenic mimicry
Sun, H., Zhang, D., Yao, Z., Lin, X., Liu, J., Gu, Q., Dong, X., Liu, F., Wang, Y., Yao, N., et al. (2017) · Cancer Biology & Therapy · doi:10.1080/15384047.2017.1294288 · Cited by 100
Triple Negative Breast Cancer: A Mountain Yet to Be Scaled Despite the Triumphs
Wu, Q., Siddharth, S., & Sharma, D. (2021) · Cancers · doi:10.3390/cancers13153697 · Cited by 110
Novel strategies for cancer immunotherapy: counter-immunoediting therapy
Liu, S., Sun, Q., & Ren, X. (2023) · Journal of Hematology & Oncology · doi:10.1186/s13045-023-01430-8 · Cited by 107
“Early anti-angiogenic drugs, mainly single-target drugs against VEGF/VEFGR, are ineffective, and many patients exhibit resistance to them [45, 46].”
BackgroundAnti-angiogenesis in cancer therapy: Hercules and hydra
Bellou, S., Pentheroudakis, G. E., Murphy, C., & Fotsis, T. (2013) · Cancer Letters · doi:10.1016/j.canlet.2013.05.015 · Cited by 98
“However, hypoxic conditions, caused by anti-angiogenic therapy, are capable of recruiting bone marrow-derived cells (BMDCs) that include vascular progenitors (endothelial and pericyte progenitors) and vascular modulatory cells (tumour associated macrophages, immature monocytic cells and myeloid cells) [53].”
BackgroundSong, G. K., Darr, D. B., Santos, C., Ross, M., Valdivia, A., Jordan, J. L., Midkiff, B. R., Cohen, S. M., Nikolaishvili‐Feinberg, N., Miller, C. R., et al. (2014) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-14-0493 · Cited by 100
Engineered Multifunctional Nanocarriers for Cancer Diagnosis and Therapeutics
Shi, D., Bedford, N. M., & Cho, H. (2011) · Small · doi:10.1002/smll.201100436 · Cited by 99
Schnegg, C. I., Yang, M. H., Ghosh, S. K., & Hsu, M. (2015) · Cancer Research · doi:10.1158/0008-5472.can-14-1855 · Cited by 99
“Discussion As melanomas are heterogeneous in the clinical setting, some melanomas initially respond to antiVEGF therapy but eventually develop clinical resistance, the so-called “initial responders”, while other melanomas are intrinsically resistant and do not respond to anti-VEGF therapy (4-6).”
BackgroundIcli, B., Wu, W. W., Ozdemir, D., Li, H., Cheng, H. S., Haemmig, S., Liu, X. Z., Giatsidis, G., Avci, S. N., Lee, N., et al. (2019) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.119.312726 · Cited by 99
Ribatti, D., Solimando, A. G., & Pezzella, F. (2021) · Cancers · doi:10.3390/cancers13143433 · Cited by 99
“Consequently, PDAC is difficult to treat with anti-angiogenics; therefore, novel approaches have attempted to combine immune-directed therapies to peculiar invasive phenotypes [64,78,80].”
BackgroundNADPH Oxidases as Regulators of Tumor Angiogenesis: Current and Emerging Concepts
Coso, S., Harrison, I., Harrison, C. B., Vinh, A., Sobey, C. G., Drummond, G. R., Williams, E. D., & Selemidis, S. (2012) · Antioxidants and Redox Signaling · doi:10.1089/ars.2011.4489 · Cited by 101
“The second suggests that angiogenesis and the revascularization after conventional antiangiogenic drug therapy are caused by chronic inflammation (18, 33, 127).”
Development of Molecularly Targeted Therapies in Hepatocellular Carcinoma: Where Do We Go Now?
Finn, R. S. (2010) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-09-2084 · Cited by 99
Optimal Management of Metastatic Renal Cell Carcinoma: Current Status
Escudier, B. J., Albiges, L. K., & Sonpavde, G. (2013) · Drugs · doi:10.1007/s40265-013-0043-1 · Cited by 98
“upregulate HIF (Hypoxia Inducible Factor), a transcription factor that binds to DNA and leads to the production of multiple proangiogenic molecules including VEGF [5].”
BackgroundConvergence of VEGF and YAP/TAZ signaling: Implications for angiogenesis and cancer biology
Elaimy, A. L., & Mercurio, A. M. (2018) · Science Signaling · doi:10.1126/scisignal.aau1165 · Cited by 100
“This observation may explain, in part, the dismal efficacy of bevacizumab for many cancers (38, 39), and it highlights the potential benefit of directly targeting the NRPs as an approach to inhibiting VEGF signaling in CSCs.”
BackgroundRegulation of redox signaling in HIF‐1‐dependent tumor angiogenesis
Manuelli, V., Pecorari, C., Filomeni, G., & Zito, E. (2021) · FEBS Journal · doi:10.1111/febs.16110 · Cited by 107
The role of bone-marrow-derived cells in tumor growth, metastasis initiation and progression
Gao, D., & Mittal, V. (2009) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2009.06.006 · Cited by 99
Nanoparticulate immunotherapy for cancer
Kapadia, C. H., Perry, J. L., Tian, S., Luft, J. C., & DeSimone, J. M. (2015) · Journal of Controlled Release · doi:10.1016/j.jconrel.2015.09.062 · Cited by 98
“The benefits are at best transitory and are followed by a restoration of tumor growth and progression [97].”
BackgroundBuczek, M. E., Escudier, B. J., Bartnik, E., Szczylik, C. A., & Czarnecka, A. M. (2013) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2013.10.001 · Cited by 100
“U N C O R R E C support for vasculature in the absence of VEGF-mediated signaling, which is supported by the fact that vessels lacking pericyte coverage are more vulnerable to anti-VEGF therapy [17,53] and that pericytes are able to express considerable levels of VEGF and other factors supporting survival of endotheli…”
BackgroundResultZhang, X., Wang, Y., Fan, J., Chen, W., Luan, J., Mei, X., Wang, S., Li, Y., Ye, L., Li, S., et al. (2019) · Journal for ImmunoTherapy of Cancer · doi:10.1186/s40425-019-0812-9 · Cited by 95
Yang, Q., Lei, X., He, J., Peng, Y., Zhang, Y., Ling, R., Wu, C., Zhang, G., Zheng, B., Chen, X., et al. (2023) · Advanced Science · doi:10.1002/advs.202300898 · Cited by 97
Role of the tumor stroma in resistance to anti-angiogenic therapy
Huijbers, E. J. M., B, J. R. V. B., Thijssen, V. L., Sabrkhany, S., Nowak-Sliwinska, P. M., & Griffioen, A. W. (2016) · Drug Resistance Updates · doi:10.1016/j.drup.2016.02.002 · Cited by 97
Pham, E., Birrer, M. J., Eliasof, S. D., Garmey, E. G., Lazarus, D. D., Lee, C. R., Man, S., Matulonis, U. A., Peters, C. G., Xu, P., et al. (2014) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-14-2810 · Cited by 94
Nanomaterials targeting tumor associated macrophages for cancer immunotherapy
Zhao, C., Pang, X., Yang, Z., Wang, S., Deng, H., & Chen, X. S. (2021) · Journal of Controlled Release · doi:10.1016/j.jconrel.2021.11.028 · Cited by 98
Progress toward Overcoming Hypoxia-Induced Resistance to Solid Tumor Therapy
Reginato, M., & Karakashev, S. (2015) · Cancer Management and Research · doi:10.2147/cmar.s58285 · Cited by 95
“Although some of the patients initially responded well and had regression of primary tumors, over time tumors became resistant and in many cases the tumors become more aggressive and contain increased metastasis.(126) One possibility is that antiangiogenic therapy promotes hypoxia that activates survival, invasion and…”
Targeting the Ras–ERK pathway in pancreatic adenocarcinoma
Neuzillet, C., Hammel, P. R., Tijeras‐Raballand, A., Couvelard, A., & Raymond, É. (2012) · Cancer and Metastasis Reviews · doi:10.1007/s10555-012-9396-2 · Cited by 97
Zhang, W., Sun, H., Wang, W., Zhang, Q., Zhuang, P., Xiong, Y., Zhu, X., Xu, H., Kong, L., Wu, W., et al. (2012) · Gastroenterology · doi:10.1053/j.gastro.2012.08.032 · Cited by 95
Cenik, B. K., Ostapoff, K. T., Gerber, D. E., & Brekken, R. A. (2013) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-12-0995 · Cited by 94
“antiangiogenic therapies targeting VEGF have shown only modest clinical effect and are prone to resistance in many disease contexts (1).”
BackgroundCheng, A., Thongprasert, S., Lim, H. Y., Sukeepaisarnjaroen, W., Yang, T., Wu, C., Chao, Y., Chan, S. L., Kudo, M., Ikeda, M., et al. (2016) · Hepatology · doi:10.1002/hep.28600 · Cited by 95
“occur due to FGFR pathway activation.((22)) In addition to VEGFR and PDGFR, dovitinib inhibits FGFR((23)) and has been hypothesized to provide more effective and sustainable antitumor activity in patients with advanced HCC.”
InfluentialContribution of pericyte paracrine regulation of the endothelium to angiogenesis
Caporali, A., Martello, A., Miscianinov, V., Maselli, D., Vono, R., & Spinetti, G. (2016) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2016.10.001 · Cited by 96
“Some vessels especially those surrounding the tumor, are highly covered and this creates a sort of barrier impeding the access to the cells of the immune system and to therapeutic agents (Bergers & Hanahan, 2008).”
BackgroundTherapy for Cancer: Strategy of Combining Anti-Angiogenic and Target Therapies
Comunanza, V., & Bussolino, F. (2017) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2017.00101 · Cited by 99
“The reasons of this discrepancy have been partially understood and well addressed in many reviews (Bergers and Hanahan, 2008; Bottsford-Miller et al., 2012; El-Kenawi and El-Remessy, 2013; Wang et al., 2015; Jayson et al., 2016).”
BackgroundMissiaen, R., Mazzone, M., & Bergers, G. (2018) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2018.06.002 · Cited by 96
“These imply at least two major relapse categories, in which tumors either reinstate growth by revascularization or alter their growth behavior without obligate neovascularization [121].”
Self-citationDjokovic, D., Trindade, A., Gigante, J., Badenes, M., Silva, L., Liu, R., Li, X., Gong, M., Krasnoperov, V. G., Gill, P. S., et al. (2010) · BMC Cancer · doi:10.1186/1471-2407-10-641 · Cited by 99
“Rapid development of resistance to these [2], however, highlights the need for other vascular targeted therapies.”
BackgroundMethodCombination Strategy Targeting VEGF and HGF/c-met in Human Renal Cell Carcinoma Models
Ciamporcero, E. S., Miles, K. M., Adelaiye-Ogala, R. M., Ramakrishnan, S., Shen, L., Ku, S., Pizzimenti, S., Sennino, B., Barrera, G., & Пили, Р. (2014) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-14-0094 · Cited by 93
“upregulation of alternative proangiogenic signals, and an increase of the invasive and metastatic behavior of tumor cells have been reported to play an important role (12, 13).”
BackgroundTRPV4 channels regulate tumor angiogenesis via modulation of Rho/Rho kinase pathway
Thoppil, R. J., Cappelli, H. C., Adapala, R. K., Kanugula, A. K., Paruchuri, S. M., & Thodeti, C. K. (2016) · Oncotarget · doi:10.18632/oncotarget.8405 · Cited by 97
Damage effect of high-intensity focused ultrasound on breast cancer tissues and their vascularities
Guan, L., & Xu, G. (2016) · World Journal of Surgical Oncology · doi:10.1186/s12957-016-0908-3 · Cited by 94
“Our current inability to identify which patients truly benefit from anti-angiogenic agents may be the real reason for the survival outcome of these trials [13, 14].”
BackgroundCytosolic Phospholipase A2 and Lysophospholipids in Tumor Angiogenesis
Linkous, A. G., Yazlovitskaya, E. M., & Hallahan, D. E. (2010) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djq290 · Cited by 96
“However, although several angiogenesis inhibitors have produced an enhanced clinical benefit, many of these pharmacological agents result in only transitory improvements that are followed by increased tumor resistance (42).”
BackgroundInterferon-α as angiogenesis inhibitor: Learning from tumor models
Indraccolo, S. (2010) · Autoimmunity · doi:10.3109/08916930903510963 · Cited by 94
Resistance to Anti-angiogenic Therapies: A Mechanism Depending on the Time of Exposure to the Drugs
Montemagno, C., & Pagès, G. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.00584 · Cited by 100
“The main chemo-attractants for EPCs in tumor tissue are VEGFA and SDF1, released by ECs, cancer cells and CAFs (Orimo et al., 2005; Grunewald et al., 2006).”
BackgroundInfluentialTargeting Tie2 in the Tumor Microenvironment: From Angiogenesis to Dissemination
Duran, C. L., Borriello, L., Karagiannis, G. S., Entenberg, D. R., Oktay, M. H., & Condeelis, J. S. (2021) · Cancers · doi:10.3390/cancers13225730 · Cited by 90
Chemotherapy in metastatic renal cell carcinoma today? A systematic review
Buti, S., Bersanelli, M., Sikokis, A., Maines, F., Facchinetti, F., Bria, E., Ardizzoni, A., Tortora, G., & Massari, F. (2013) · Anti-Cancer Drugs · doi:10.1097/cad.0b013e3283609ec1 · Cited by 93
Antiangiogenic drugs in ovarian cancer
Kumaran, G., Jayson, G. C., & Clamp, A. R. (2008) · British Journal of Cancer · doi:10.1038/sj.bjc.6604767 · Cited by 93
“Several other resistance mechanisms have also been proposed including the recruitment of vascular progenitor cells and monocytes from bone marrow as well as the increased protection from better pericyte coverage (Bergers and Hanahan, 2008).”
BackgroundAngiogenesis in Neuroendocrine Tumors: Therapeutic Applications
Scoazec, J. (2012) · Neuroendocrinology · doi:10.1159/000338371 · Cited by 95
iNGR-modified PEG-PLGA nanoparticles that recognize tumor vasculature and penetrate gliomas
Kang, T., Gao, X., Hu, Q., Jiang, D., Feng, X., Zhang, X., Song, Q., Yao, L., Huang, M., Jiang, X., et al. (2014) · Biomaterials · doi:10.1016/j.biomaterials.2014.01.082 · Cited by 93
“The disappointing outcomes are probably resulted from the high complexity of tumor angiogenesis regulation and insufficient tumor cell cytotoxicity, so it is desirable to also target the tumor cells within the bulk of tumor [47,48].”
BackgroundSato, M., Yao, V. J., Arap, W., & Pasqualini, R. (2010) · Advances in genetics · doi:10.1016/s0065-2660(10)69006-2 · Cited by 92
Targeting the Angiopoietin-2/Tie-2 axis in conjunction with VEGF signal interference
Biel, N. M., & Siemann, D. W. (2014) · Cancer Letters · doi:10.1016/j.canlet.2014.09.035 · Cited by 95
“Even though VEGF is a major driver of angiogenesis there are other growth factors such as basic FGF, interleukin-8 (IL-8), PlGF, PDGF, and IGF that can compensate in the absence of VEGF pathway activation [12,59].”
BackgroundInfluentialCarbone, C., Moccia, T., Zhu, C., Paradiso, G., Budillon, A., Chiao, P. J., Abbruzzese, J. L., & Melisi, D. (2011) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-11-1185 · Cited by 92
“The X-axis represents the log (10) P value for enrichment, with the threshold drawn at P 1⁄4 0.”
Chen, P., Tang, C., Lin, L.-W., Tsai, C., Chu, C.-Y., Lin, T., & Huang, Y. (2017) · Journal of Hematology & Oncology · doi:10.1186/s13045-017-0390-6 · Cited by 93
“The development of an antiangiogenic target has been a common strategy for cancer therapy for a long time, but substantial benefits remain unrealized because tumors elicit evasive resistance [39].”
Background
Metadata
- Authors
- Bergers, G., & Hanahan, D.
- Affiliations
- University of California, San Francisco (US)
- Venue
- Nature Reviews Cancer
- Published
- 2008-08
- Volume
- 8
- Issue
- 8
- Pages
- 592-603
- ISSN
- 1474-175X (ISSN-L)
- 1474-1768
- PMC
- PMC2874834
- OpenAlex
- W2017322644
- Cited by
- 2,953
- References
- 101
- Citations by year
- 2026: 70 · 2025: 77 · 2024: 97 · 2023: 130 · 2022: 95 · 2021: 172 · 2020: 133 · 2019: 152 · 2018: 148 · 2017: 202 · 2016: 217 · 2015: 228 · 2014: 241 · 2013: 248 · 2012: 215
- FWCI
- 13.60
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature reviews. Cancer (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (R01CA099948)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Health Sciences › Medicine › Oncology › Lymphatic System and Diseases
- Keywords
- anti-angiogenic therapy, drug resistance, vascular endothelial growth factor, VEGF signaling, tumor angiogenesis, intrinsic resistance, combination therapy
- MeSH terms
- Humans, Neoplasms, Neovascularization, Pathologic, Signal Transduction, Drug Resistance, Neoplasm, Angiogenesis Inhibitors, Vascular Endothelial Growth Factors
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
