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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.
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“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]
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“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]
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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
Research works printed but not linked: 1
- Berger, M. S. & Wilson, C. B. The Gliomas (W.B. Saunders, Philadelphia, 1999).
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Sorted by citations
Items 901–1,000 of 1,005
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Jiménez, C., Fazeli, S., & Román-Gonzaléz, A. (2020) · Endocrine Related Cancer · doi:10.1530/erc-20-0043 · Cited by 54
“…drug concentrations that increase hypoxia, promoting tumor progression and spread, (6) activation of pathways that lead to tumor spread (c-met pathway), and (7) tumor symbiosis mediated by overactivation of mammalian target of rapamycin (mTOR) signaling (Bergers & Hanahan 2008, Zarrin et al.”
BackgroundDecoding Tumor Angiogenesis for Therapeutic Advancements: Mechanistic Insights
Kaur, G., & Roy, B. (2024) · Biomedicines · doi:10.3390/biomedicines12040827 · Cited by 56
“Tumors can activate compensatory angiogenesis pathways, such as the upregulation of alternative proangiogenic factors like fibroblast growth factor (FGF) or platelet-derived growth factor (PDGF), to bypass the inhibition of VEGF signaling [123].”
BackgroundSidhic, J., Kuttithodi, A. M., Prasad, A., Tom, A., Mohan, P., Sarbadhikary, P., Narayanankutty, A., George, S., Abrahamse, H., & George, B. P. A. (2025) · Journal of Drug Delivery Science and Technology · doi:10.1016/j.jddst.2025.106622 · Cited by 52
Womeldorff, M. R., Gillespie, D. L., & Jensen, R. L. (2014) · Neurosurgical FOCUS · doi:10.3171/2014.9.focus14496 · Cited by 51
Bhattacharya, A. (2011) · Expert Opinion on Drug Delivery · doi:10.1517/17425247.2011.571672 · Cited by 50
“Thus, with antiVEGF therapy, some patients show limited survival advantage, other cases show no such benefits or an inevitable disease progression, indicating an intrinsic resistance and/or an adaptive response of tumors against such agents [35].”
BackgroundSoluble forms of VEGF receptor‐1 and ‐2 promote vascular maturation via mural cell recruitment
Lorquet, S., Berndt, S., Blacher, S., Gengoux, E., Peulen, O., Maquoi, E., Noël, A., Foidart, J., Munaut, C., & Péqueux, C. (2010) · The FASEB Journal · doi:10.1096/fj.09-149070 · Cited by 50
“Altogether, our results sustain that physiological antiVEGF, sVEGFR-1, is involved in the interaction between EC and PC/SMC that promotes the recruitment of mural cells, similarly to what was reported for other inhibitors of the VEGF axis (9, 10, 46).”
BackgroundResultThe Future of Targeted Therapies in Ovarian Cancer
Banerjee, S. N., & Gore, M. E. (2009) · The Oncologist · doi:10.1634/theoncologist.2009-0013 · Cited by 50
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Brunckhorst, M. K., Yin, X., Lu, R., & Yu, Q. (2014) · American Journal Of Pathology · doi:10.1016/j.ajpath.2014.05.006 · Cited by 50
Angiogenesis in NSCLC: is vessel co-option the trunk that sustains the branches?
Coelho, A., Gomes, M. P., Catarino, R., Rolfo, C. D., Lopes, A. M., Medeiros, R., & Araújo, A. (2016) · Oncotarget · doi:10.18632/oncotarget.7794 · Cited by 50
Zhang, H., Tian, Y., Zhu, Z., Xu, H., Li, X., Zheng, D., & Sun, W. (2016) · Scientific Reports · doi:10.1038/srep26546 · Cited by 50
Acquired tumor resistance to antiangiogenic therapy: Mechanisms at a glance
Zarin, B., Zarifi, F., Vaseghi, G., & Javanmard, S. H. (2017) · Journal of Research in Medical Sciences · doi:10.4103/jrms.jrms_182_17 · Cited by 50
“Differentiated ECs from their progenitors (EPC) under VEGF and SDF1 chemotactic factors secretion, incorporate into newly forming blood vessels.[19]”
BackgroundControl of Blood Vessel Formation by Notch Signaling
Tetzlaff, F., & Fischer, A. (2018) · Advances in experimental medicine and biology · doi:10.1007/978-3-319-89512-3_16 · Cited by 52
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Angioni, R., Liboni, C., Herkenne, S., Sánchez‐Rodríguez, R., Borile, G., Marcuzzi, E., Calì, B., Muraca, M., & Viola, A. (2020) · Journal of Extracellular Vesicles · doi:10.1080/20013078.2020.1757900 · Cited by 49
“nomas have been treated with sunitinib and sorafenib, respectively [116].”
BackgroundThe CXCL2/IL8/CXCR2 Pathway Is Relevant for Brain Tumor Malignancy and Endothelial Cell Function
Urbantat, R. M., Blank, A., Kremenetskaia, I., Vajkoczy, P., Acker, G., & Brandenburg, S. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22052634 · Cited by 50
“However, therapeutic approaches targeting the VEGF/VEGFR pathway in GBM did not lead to a prolonged overall survival due to a range of resistance mechanisms [10,11,18,45].”
BackgroundSunitinib and other targeted therapies for renal cell carcinoma
Powles, T. B., Chowdhury, S., Jones, R. J., Mantle, M., Nathan, P., Bex, A., Lim, L., & Hutson, T. E. (2011) · British Journal of Cancer · doi:10.1038/sj.bjc.6606061 · Cited by 49
“Specifically, FGF-2, tie2/Ang2, il-8 and the Src family have been implicated in this process (Oliner et al, 2004; Cenni et al, 2005; Bergers and Hanahan 2008).”
Herzog, A. E., Warner, K. A., Zhang, Z., Bellile, E. L., Bhagat, M. A., CASTILHO, R. M., Wolf, G. T., Polverini, P. J., Pearson, A. T., & Nor, J. E. (2021) · Cell Death and Disease · doi:10.1038/s41419-021-04268-5 · Cited by 49
Modulating cancer mechanopathology to restore vascular function and enhance immunotherapy
Mpekris, F., Panagi, M., Charalambous, A., Voutouri, C., & Stylianopoulos, T. (2024) · Cell Reports Medicine · doi:10.1016/j.xcrm.2024.101626 · Cited by 55
Nitration of Hsp90 on Tyrosine 33 Regulates Mitochondrial Metabolism
Franco, M. C., Ricart, K. C., González, A. S., Dennys, C. N., Nelson, P. A., Janes, M. S., Mehl, R. A., Landar, A. L., & Estévez, Á. G. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.663278 · Cited by 49
“Tyrosine nitration is present in vivo in malignant gliomas (7) and in invasive breast carcinomas (9) where anti-angiogenic therapies have had very limited success (54, 55).”
BackgroundAmer, M. S., McKeown, L., Tumova, S., Liu, R., Seymour, V. A. L., Wilson, L. A., Naylor, J., Greenhalgh, K., Hou, B., Majeed, Y., et al. (2012) · British Journal of Pharmacology · doi:10.1111/bph.12041 · Cited by 50
“Clinical trials have shown benefit of VEGF antagonism in cancer treatment, albeit with problems of resistance and limited efficacy (Bergers and Hanahan, 2008).”
Chen, C., Cheng, C.-T., Yuan, Y., Zhai, J., Arif, M., Fong, L. W. R., Wu, R., & Ann, D. K. (2015) · Oncotarget · doi:10.18632/oncotarget.3827 · Cited by 52
Angiogenesis in Spontaneous Tumors and Implications for Comparative Tumor Biology
Benazzi, C., Al-Dissi, A. N., Chau, C. H., Figg, W. D., Sarli, G., Oliveira, J., & Gärtner, F. (2014) · The Scientific World JOURNAL · doi:10.1155/2014/919570 · Cited by 53
Zurita, A. J., Khajavi, M., Wu, H.-K., Tye, L., Huang, X., Kulke, M. H., Lenz, H. J., Meropol, N. J., Carley, W. W., DePrimo, S. E., et al. (2015) · British Journal of Cancer · doi:10.1038/bjc.2015.73 · Cited by 49
“Second, myelomonocytic cells under different designations facilitate angiogenesis, tumour progression, and metastasis (Bergers and Hanahan, 2008; Du et al, 2008).”
BackgroundMethodInfluentialTargeting multiple kinases in glioblastoma multiforme
Sathornsumetee, S., & Reardon, D. A. (2009) · Expert Opinion on Investigational Drugs · doi:10.1517/13543780802692603 · Cited by 49
“Increases in viable circulating endothelial cells, basic fibroblast growth factor (FGF) and stromal derived factor (SDF) 1 α levels were observed during disease progression suggesting that upregulation of other pro-angiogenic factors may underlie pathogenesis of acquired resistance to VEGFR-directed therapy [40] .”
BackgroundChange in Pattern of Relapse After Antiangiogenic Therapy in High-Grade Glioma
Narayana, A., Kunnakkat, S., Medabalmi, P., Golfinos, J. G., Parker, E. C., Knopp, E. A., Zagzag, D., Eagan, P., Gruber, D., & Gruber, M. L. (2010) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/j.ijrobp.2010.10.038 · Cited by 49
Puré, E. (2009) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728220903103841 · Cited by 49
“Indeed, introduction of antiangiogenic drugs, based on this paradigm, has had a clinical impact in some tumor types, as have cancer immunotherapies [1-3].”
BackgroundKudo, M. (2012) · World Journal of Gastroenterology · doi:10.3748/wjg.v18.i42.6005 · Cited by 49
Piscazzi, A., Costantino, E., Maddalena, F., Natalicchio, M. I., Gerardi, A. M. T., Antonetti, R., Cignarelli, M., & Landriscina, M. (2012) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2011-3269 · Cited by 49
“Furthermore, because the increased expression of alternative growth factors with proangiogenic potential and capable of directly stimulating tumor cells has been proposed as an escape mechanism from anti-vascular endothelial growth factor therapies (21), we hypothesized that epithelial growth factor (EGF), which is kn…”
BackgroundBridgeman, V. L., Wan, E., Foo, S., Nathan, M. R., Welti, J. C., Frentzas, S., Vermeulen, P., Preece, N., Springer, C. J., Powles, T. B., et al. (2015) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-15-0170 · Cited by 49
Treps, L., Conradi, L., Harjes, U., & Carmeliet, P. (2016) · Pharmacological Reviews · doi:10.1124/pr.116.012492 · Cited by 52
“…agents targeting VEGF signaling often fails to yield sustained responses, because themajority of patients develop resistance (Schneider and Sledge, 2007; Bergers and Hanahan, 2008; Cortes-Funes, 2009; Grothey and Galanis, 2009; Mackey et al., 2012; He andGoldenberg, 2013; Vincent et al., 2015).”
BackgroundExosomes in Tumor Angiogenesis
Salem, K. Z., Moschetta, M., Sacco, A., Imberti, L., Rossi, G., Ghobrial, I. M., Manier, S., & Roccaro, A. M. (2016) · Methods in molecular biology · doi:10.1007/978-1-4939-3999-2_3 · Cited by 50
EGFL7 enhances surface expression of integrin α5β1 to promote angiogenesis in malignant brain tumors
Stanković, N. D., Bicker, F., Keller, S., Jones, D., Harter, P. N., Kienzle, A., Gillmann, C., Arnold, P., Golebiewska, A., Keunen, O., et al. (2018) · EMBO Molecular Medicine · doi:10.15252/emmm.201708420 · Cited by 52
“These disillusioning results may be due to tumor adaptation and exploitation of alternative angiogenesis pathways upon bevacizumab treatment (Bergers & Hanahan, 2008; Keunen et al, 2011).”
BackgroundTargeting HIBCH to reprogram valine metabolism for the treatment of colorectal cancer
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Tyrosine kinase inhibitors and the thyroid
Sherman, S. I. (2009) · Best Practice & Research Clinical Endocrinology & Metabolism · doi:10.1016/j.beem.2009.08.001 · Cited by 50
Decrease in VEGF Expression Induces Intussusceptive Vascular Pruning
Hlushchuk, R., Ehrbar, M., Reichmuth, P., Heinimann, N., Styp‐Rekowska, B., Escher, R., Baum, O., Lienemann, P. S., Makanya, A. N., Keshet, E., et al. (2011) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.111.231811 · Cited by 49
Peng, C., Tian, Q., Yang, G., Fang, M., Zhang, Z., Peng, J., Li, Y., & Pang, D. (2012) · Biomaterials · doi:10.1016/j.biomaterials.2012.04.034 · Cited by 49
“Therefore, maturity and normalization of neoangiogenesis have become the focus of intensive investigation [19].”
Yin, J. J., Zhang, L., Munasinghe, J., Linnoila, R. I., & Kelly, K. (2010) · Cancer Research · doi:10.1158/0008-5472.can-10-1435 · Cited by 48
The role of core TNF/LIGHT family members in lymph node homeostasis and remodeling
Zhu, M., & Fu, Y. (2011) · Immunological Reviews · doi:10.1111/j.1600-065x.2011.01061.x · Cited by 48
“In both preclinical and clinical settings, the benefits are at best transitory and are followed by a restoration of tumor growth and progression (62).”
BackgroundAdvances in treating glioblastoma
Weathers, S.-P. S., & Gilbert, M. R. (2014) · F1000Prime Reports · doi:10.12703/p6-46 · Cited by 50
“Adaptive (evasive) resistance and intrinsic (pre-existing) non-responsiveness have emerged as the modes of resistance to antiangiogenic therapy, with multiple mechanisms believed to underlie each type [29].”
InfluentialVascular Targeted Radioimmunotherapy for the Treatment of Glioblastoma
Behling, K., Maguire, W. F., Puebla, J. C. L., Sprinkle, S. R., Ruggiero, A., O’Donoghue, J. A., Gutin, P. H., Scheinberg, D. A., & McDevitt, M. R. (2016) · Journal of Nuclear Medicine · doi:10.2967/jnumed.115.171371 · Cited by 49
“However, systemic toxicity has been an important issue when treating with bevacizumab (7), as well as observed resistance to the treatment (8) and only minimally improved survival benefit.”
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Kwiatkowski, S. C., Guerrero, P. A., Hirota, S., Chen, Z., Morales, J. E., Aghi, M. K., & McCarty, J. H. (2017) · PLoS ONE · doi:10.1371/journal.pone.0185065 · Cited by 48
Osako, Y., Yoshino, H., Sakaguchi, T., Sugita, S., Yonemori, M., Nakagawa, M., & Enokida, H. (2019) · International Journal of Oncology · doi:10.3892/ijo.2019.4736 · Cited by 50
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Xiao, W., Wang, X., Wang, T., & Xing, J. (2019) · Cancer Gene Therapy · doi:10.1038/s41417-019-0107-9 · Cited by 50
Pal, K., Madamsetty, V. S., Dutta, S. K., Wang, E., Angom, R. S., & Mukhopadhyay, D. (2019) · npj Precision Oncology · doi:10.1038/s41698-019-0105-2 · Cited by 47
“However, patients ultimately became resistant towards the antiangiogenic therapies, thus limiting the long-term benefits.(23) In addition to the above anti-VEGF treatments, several other routes have been evaluated for antiangiogenic therapy.”
BackgroundTumor-Associated Fibroblasts as “Trojan Horse” Mediators of Resistance to Anti-VEGF Therapy
Francia, G., Emmenegger, U., & Kerbel, R. S. (2009) · Cancer Cell · doi:10.1016/j.ccr.2008.12.011 · Cited by 48
“As a result, a rapidly growing area in tumor angiogenesis research is the elucidation of the mechanisms responsible for both intrinsic and acquired resistance to antiangiogenic agents (Bergers and Hanahan, 2008).”
BackgroundResch, T., Pircher, A., Kähler, C. M., Pratschke, J., & Hilbe, W. (2011) · Stem Cell Reviews and Reports · doi:10.1007/s12015-011-9332-9 · Cited by 49
A cluster of long non-coding RNAs exhibit diagnostic and prognostic values in renal cell carcinoma
Cheng, G., Liu, D., Liang, H., Yang, H., Chen, K., & Zhang, X. (2019) · Aging · doi:10.18632/aging.102407 · Cited by 47
“Targeted therapies have recently been administered to patients with ccRCC, but the overall survival (OS) of patients at the terminal stage of the disease has not been as good as expected [9].”
BackgroundERK and c-Myc signaling in host-derived tumor endothelial cells is essential for solid tumor growth
Zuo, Z., Liu, J., Sun, Z., Cheng, Y., Ewing, M., Bugge, T. H., Finkel, T., Leppla, S. H., & Liu, S. (2022) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2211927120 · Cited by 47
The circadian protein BMAL1 supports endothelial cell cycle during angiogenesis
Astone, M., Oberkersch, R. E., Tosi, G., Biscontin, A., & Santoro, M. M. (2023) · Cardiovascular Research · doi:10.1093/cvr/cvad057 · Cited by 49
Anti‐angiogenesis in colorectal cancer therapy
Yang, Z., Zhang, X., Bai, X., Xi, X., Liu, W., & Zhong, W. (2024) · Cancer Science · doi:10.1111/cas.16063 · Cited by 50
“28,239,240 Compensatory pathways in angiogenesis are nonnegligible in DR. TGF-β , FGF 2, PDGF, Ang-2, and IL-1 are assumed to be highly relevant to anti-VEGF resistance in cancer.”
BackgroundClass 3 semaphorins: physiological vascular normalizing agents for anti‐cancer therapy
Serini, G., Bussolino, F., Maione, F., & Giraudo, E. (2013) · Journal of Internal Medicine · doi:10.1111/joim.12017 · Cited by 48
Limitations of therapies exposed
Casanovas, O. (2012) · Nature · doi:10.1038/484044a · Cited by 46
Bevacizumab for Malignant Gliomas
IWAMOTO, F. M., & Fine, H. A. (2010) · Archives of Neurology · doi:10.1001/archneurol.2010.11 · Cited by 47
“Furthermore, mechanisms of resistance to antiangiogenic therapies should be investigated.(25,29) Clinical,(30) molecular,(31) and/or radiographic markers(32) to identify patients more likely to respond to antiangiogenic therapies need to be validated.”
BackgroundZheng, X., Koh, G. Y., & Jackson, T. L. (2013) · Discrete and Continuous Dynamical Systems - B · doi:10.3934/dcdsb.2013.18.1109 · Cited by 47
“However, the clinical benefits are transitory and are followed by a restoration of tumor growth and progression [14, 35].”
BackgroundSynergistic effects of IAP inhibitor LCL161 and paclitaxel on hepatocellular carcinoma cells
Tian, A., Wilson, G. S., Lie, S., Wu, G. J., Hu, Z., Hebbard, L., Duan, W., George, J., & Qiao, L. (2014) · Cancer Letters · doi:10.1016/j.canlet.2014.06.006 · Cited by 47
Bousquet, G., Alexandre, J., Tourneau, C. L., Goldwasser, F., Faivre, S. J., de Mont-Serrat, H., Kaiser, R., Misset, J. L., & Raymond, É. (2011) · British Journal of Cancer · doi:10.1038/bjc.2011.440 · Cited by 47
“In several preclinical models, FGFR activation has been proposed as a mechanism that compensates for VEGFR inhibition in resistant tumours (Bergers and Hanahan, 2008).”
BackgroundEscape mechanisms after antiangiogenic treatment, or why are the tumors growing again?
Hlushchuk, R., Makanya, A. N., & Djonov, V. (2011) · The International Journal of Developmental Biology · doi:10.1387/ijdb.103231rh · Cited by 47
Pham, K., Luo, D., Siemann, D. W., Law, B. K., Reynolds, B. A., Hothi, P., Foltz, G., & Harrison, J. K. (2015) · Cancer Letters · doi:10.1016/j.canlet.2015.02.005 · Cited by 49
“Under VEGF pathway inhibition with Bevacizumab, a statistically significant increase in infiltrative tumor progression was identified in Bevacizumab responders [14].”
BackgroundZhou, J., Wang, H., Zhang, H., Lutz, A. M., Tian, L., Hristov, D. H., & Willmann, J. K. (2016) · Cancer Research · doi:10.1158/0008-5472.can-15-3271 · Cited by 47
“Although clinical trials have shown that anti-angiogenic therapy, either alone or in combination with first-line chemotherapy, is beneficial in several cancers including colon cancer(5), lung cancer (31)and hepatocellular carcinoma(32), resistance to angiogenic inhibitors may occur; this can lead to disease recurrence…”
BackgroundLorusso, L., Pieruzzi, L., Biagini, A., Sabini, E., Valerio, L., Giani, C., Passannanti, P., Contillo, B. P., Battaglia, V., Mazzeo, S., et al. (2016) · OncoTargets and Therapy · doi:10.2147/ott.s84625 · Cited by 47
Faes, S., Santoro, T., Demartines, N., & Dormond, O. (2017) · Cancers · doi:10.3390/cancers9110152 · Cited by 48
“For instance, the stimulation of tumor endothelial cells by other growth factors than VEGF has been identified [83,84].”
BackgroundCellular and Molecular Heterogeneity Associated with Vessel Formation Processes
Castro, P. R., Barbosa, A. S., Pereira, J. M., Ranfley, H., Felipetto, M., Gonçalves, C. A. X., Paiva, I. R., Berg, B. B., & Barcelos, L. S. (2018) · BioMed Research International · doi:10.1155/2018/6740408 · Cited by 47
Cyclooxygenase-2 blockade can improve efficacy of VEGF-targeting drugs
Batalla, I. B., Cubas‐Cordova, M., Udonta, F., Wroblewski, M., Waizenegger, J. S., Janning, M., Sawall, S., Gensch, V., Zhao, L., Martínez-Zubiaurre, I., et al. (2015) · Oncotarget · doi:10.18632/oncotarget.3437 · Cited by 47
JuanYin, J., Tracy, K. M., Zhang, L., Munasinghe, J., Shapiro, E. M., Koretsky, A. P., & Kelly, K. (2009) · Clinical & Experimental Metastasis · doi:10.1007/s10585-009-9238-y · Cited by 46
“In various preclinical models of primary or metastatic brain tumors, co-option of pre-existing vessels frequently has been observed in tumor progression or response to antiangiogenic therapy [ 9 ].”
BackgroundKoyanagi, T., Suzuki, Y., Saga, Y., 町田, 静., Takei, Y., Fujiwara, H., Suzuki, M., & Sato, Y. (2013) · Cancer Science · doi:10.1111/cas.12297 · Cited by 46
Huang, C., Wang, S.-Y., Lin, L., Wang, P., Chen, T., Hsu, W., Lin, T., Liou, C., & Chuang, J. (2015) · Disease Models & Mechanisms · doi:10.1242/dmm.021667 · Cited by 45
“It is not surprising that targeting of vascular sprouts could provide a new opportunity to improve anti-angiogenic therapy in cancer (Bergers and Hanahan, 2008; Rivera and Bergers, 2014).”
BackgroundLee, D., Kim, D., Choi, Y. B., Kang, K., Sung, E.-S., Ahn, J.-H., Goo, J.-S., Yeom, D.-H., Jang, H. S., Moon, K. D., et al. (2016) · mAbs · doi:10.1080/19420862.2016.1171432 · Cited by 46
Gangjee, A., Pavana, R. K., Ihnat, M. A., Thorpe, J. E., Disch, B. C., Bastian, A., Bailey‐Downs, L. C., Hamel, E., & Bai, R. (2014) · ACS Medicinal Chemistry Letters · doi:10.1021/ml4004793 · Cited by 46
Lodola, F., Laforenza, U., Cattaneo, F., Ruffinatti, F. A., Poletto, V., Massa, M., Tancredi, R. J., Zuccolo, E., Kheder, D. A., Riccardi, A., et al. (2017) · Oncotarget · doi:10.18632/oncotarget.20255 · Cited by 46
“Also, a minority of cancer patients are intrinsically resistant to angiogenesis blockade, such that disease progression continues unabated and leads to patient death [11].”
Guarnaccia, L., Navone, S. E., Trombetta, E., Cordiglieri, C., Cherubini, A., Crisà, F. M., Rampini, P. M., Miozzo, M. R., Fontana, L., Caroli, M., et al. (2018) · Scientific Reports · doi:10.1038/s41598-018-27116-7 · Cited by 48
Vascular co‐option and vasculogenic mimicry mediate resistance to antiangiogenic strategies
Pezzella, F., & Ribatti, D. (2020) · Cancer Reports · doi:10.1002/cnr2.1318 · Cited by 45
“It can be intrinsic, when it is observed at the beginning of the treatment, or acquired, that is, that it affects the relapsing disease after an initial response to therapy.(35,36) Following the first description of a putative mechanism, that is, the nonangiogenic cancer growth and progression by exploiting the preexi…”
BackgroundMa, S., Mangala, L. S., Hu, W. S., Bayaktar, E., Yokoi, A., Hu, W., Pradeep, S., Lee, S., Piehowski, P., Villar‐Prados, A., et al. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.109549 · Cited by 48
More than a scaffold: Stromal modulation of tumor immunity
Johansson, A., Hamzah, J., & Ganß, R. (2015) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2015.06.001 · Cited by 47
“Rapid tumor relapse or metastatic spread after anti-angiogenesis therapy and killing of endothelial cells or pericytes is an equally disappointing outcome [129,130].”
BackgroundEmerging antiangiogenic treatments for gliomas – efficacy and safety issues
Dietrich, J., Norden, A. D., & Wen, P. Y. (2008) · Current Opinion in Neurology · doi:10.1097/wco.0b013e3283131370 · Cited by 48
Nishio, M., Horai, T., Horiike, A., Nokihara, H., Yamamoto, N., Takahashi, T., Murakami, H., Yamamoto, N., Koizumi, F., Nishio, K., et al. (2013) · British Journal of Cancer · doi:10.1038/bjc.2013.374 · Cited by 47
“SDF1a, SCF, and G-CSF may have a role in recruiting these cells to angiogenic sites, thereby contributing to resistance to chemotherapy and antiangiogenic therapy (Bergers and Hanahan, 2008; Shaked et al, 2008).”
BackgroundTudisco, L., Ragione, F. D., Tarallo, V., Apicella, I., D’Esposito, M., Matarazzo, M. R., & Falco, S. D. (2014) · Epigenetics · doi:10.4161/epi.27835 · Cited by 47
Integrin-Mediated Cell-Matrix Interaction in Physiological and Pathological Blood Vessel Formation
Niland, S., & Eble, J. A. (2011) · Journal of Oncology · doi:10.1155/2012/125278 · Cited by 46
Takano, S. (2012) · Brain Tumor Pathology · doi:10.1007/s10014-011-0077-6 · Cited by 47
Therapeutic targeting of platelet-derived growth factor receptors in solid tumors
Ehnman, M., & Östman, A. (2013) · Expert Opinion on Investigational Drugs · doi:10.1517/13543784.2014.847086 · Cited by 45
“However, adaptive evasion and intrinsic non-responsiveness are of major concerns [1-3].”
BackgroundSwanton, C., Larkin, J., Gerlinger, M., Eklund, A. C., Howell, M. T., Stamp, G., Downward, J., Gore, M. E., Futreal, P. A., Escudier, B. J., et al. (2010) · Genome Medicine · doi:10.1186/gm174 · Cited by 45
“Hypoxia resistance and inherent tolerability to hypovascular environments have been observed in some cancer types [19].”
Inhibition of carbonic anhydrase potentiates bevacizumab treatment in cholangiocarcinoma
Vaeteewoottacharn, K., Kariya, R., Dana, P., Fujikawa, S., Matsuda, K., Ohkuma, K., Kudo, E., Kraiklang, R., Wongkham, C., Wongkham, S., et al. (2016) · Tumor Biology · doi:10.1007/s13277-016-4785-8 · Cited by 45
Identification of the S100 fused-type protein hornerin as a regulator of tumor vascularity
Gutknecht, M. F., Seaman, M. E., Ning, B., Cornejo, D. A., Mugler, E., Antkowiak, P. F., Moskaluk, C. A., Hu, S. N., Epstein, F. H., & Kelly, K. A. (2017) · Nature Communications · doi:10.1038/s41467-017-00488-6 · Cited by 45
Periostin Limits Tumor Response to VEGFA Inhibition
Keklikoglou, I., Kadioglu, E., Bissinger, S., Langlois, B., Bellotti, A., Orend, G., Ries, C. H., & Palma, M. D. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.02.035 · Cited by 45
Carvalho, N. D., Welzel, J., Schuh, S., Themstrup, L., Ulrich, M., Jemec, G. B. E., Holmes, J. D., Kaleci, S., Chester, J., Bigi, L., et al. (2018) · Experimental Dermatology · doi:10.1111/exd.13783 · Cited by 45
Dubinski, D., Hattingen, E., Senft, C., Seifert, V., Peters, K. G., Reiss, Y., Devraj, K., & Plate, K. H. (2019) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x19859847 · Cited by 46
Parallels of Resistance between Angiogenesis and Lymphangiogenesis Inhibition in Cancer Therapy
Jones, D. (2020) · Cells · doi:10.3390/cells9030762 · Cited by 44
“Pro-angiogenic monocytes recruited from the bone marrow promote tumor vascularizati n, gr wth, and cause resi tance to therapy [17].”
BackgroundInfluentialXie, W., Zhao, H., Wang, F., Wang, Y., He, Y. Z., Wang, T., Zhang, K., Yang, H., Zhou, Z., Shi, H., et al. (2021) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-020-01800-x · Cited by 45
Planel, S., Salomon, A., Jalinot, P., Feige, J., & Cherradi, N. (2010) · Oncogene · doi:10.1038/onc.2010.341 · Cited by 45
“However, despite the initial enthusiasm predicting the absence of resistance to these antiangiogenic treatments, such resistance appeared to occur on time (Bergers and Hanahan, 2008).”
BackgroundTumor angiogenesis and anti-angiogenic therapy
Guo, Z., Xu, J., Sun, X., Sun, S., Yang, Y., & Cao, Y. (2024) · Chinese Medical Journal · doi:10.1097/cm9.0000000000003231 · Cited by 48
Phase I study of bevacizumab, everolimus, and panobinostat (LBH-589) in advanced solid tumors
Strickler, J. H., Starodub, A., Jia, J., Meadows, K. L., Nixon, A. B., Dellinger, A. E., Morse, M. A., Uronis, H. E., Marcom, P. K., Zafar, S. Y., et al. (2012) · Cancer Chemotherapy and Pharmacology · doi:10.1007/s00280-012-1911-1 · Cited by 44
“One proposed mechanism is compensatory upregulation of other pro-angiogenic signals [5].”
Moccia, F. D., & Poletto, V. (2014) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2014.10.024 · Cited by 44
Zhang, H., Ren, Y. T., Tang, X., Wang, K., Liu, Y., Zhang, L. R., Li, X., Liu, P., Zhao, C., & He, J. (2015) · Scientific Reports · doi:10.1038/srep08888 · Cited by 44
Therapy and prophylaxis of brain metastases
Kienast, Y., & Winkler, F. (2010) · Expert Review of Anticancer Therapy · doi:10.1586/era.10.165 · Cited by 44
Busch, J. F., Seidel, C. A., Kempkensteffen, C., Johannsen, M., Wolff, I., Hinz, S., Magheli, A., Miller, K., Grünwald, V., & Weikert, S. (2011) · European Urology · doi:10.1016/j.eururo.2011.07.037 · Cited by 44
“Evasive or acquired tumour resistance may develop via mechanisms like alternative proangiogenic signalling pathways within the tumour, recruitment of bone marrow–derived proangiogenic cells, increasedprotection of tumour vasculature by pericytes, and increased tumour cell invasiveness to escape oxygen and nutrient dep…”
BackgroundHuang, X., Chau, C. H., & Figg, W. D. (2012) · Journal of Hematology & Oncology · doi:10.1186/1756-8722-5-35 · Cited by 45
“Indeed, blocking neovascularization by VEGF antibody was found to induce hypoxia which in turn up-regulate angiogenic factors such as bFGF, chemokines and ephrin, and angiopoietin families, leading to anti-angiogenesis rescue [57].”
BackgroundTargeting tumour vasculature by inhibiting activin receptor-like kinase (ALK)1 function
de Vinuesa, A. G., Bocci, M., Pietras, K., & ten Dijke, P. (2016) · Biochemical Society Transactions · doi:10.1042/bst20160093 · Cited by 44
“However, despite the initial success and improvement in response rate in several cancers, the overall survival is only modestly improved and resistance to therapy often develops due to activation of alternative pathways ([29]).”
BackgroundRecurrent glioblastoma: a fresh look at current therapies and emerging novel approaches
Gilbert, M. R. (2011) · Seminars in Oncology · doi:10.1053/j.seminoncol.2011.09.008 · Cited by 45
Recent advances of dual FGFR inhibitors as a novel therapy for cancer
Liang, Q., Wang, J., Zhao, L., Hou, J., Hu, Y., & Shi, J. (2021) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2021.113205 · Cited by 32
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
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