Go to
JCI Insight
Citations to this article
Monika Haemmerle, … , Vahid Afshar-Kharghan, Anil K. Sood
Published April 11, 2016
Citation Information: J Clin Invest. 2016;126(5):1885-1896. https://doi.org/10.1172/JCI85086.
Citation Information: J Clin Invest. 2016;126(5):1885-1896. https://doi.org/10.1172/JCI85086.
Abstract
Recent studies in patients with ovarian cancer suggest that tumor growth may be accelerated following cessation of antiangiogenesis therapy; however, the underlying mechanisms are not well understood. In this study, we aimed to compare the effects of therapy withdrawal to those of continuous treatment with various antiangiogenic agents. Cessation of therapy with pazopanib, bevacizumab, and the human and murine anti-VEGF antibody B20 was associated with substantial tumor growth in mouse models of ovarian cancer. Increased tumor growth was accompanied by tumor hypoxia, increased tumor angiogenesis, and vascular leakage. Moreover, we found hypoxia-induced ADP production and platelet infiltration into tumors after withdrawal of antiangiogenic therapy, and lowering platelet counts markedly inhibited tumor rebound after withdrawal of antiangiogenic therapy. Focal adhesion kinase (FAK) in platelets regulated their migration into the tumor microenvironment, and FAK-deficient platelets completely prevented the rebound tumor growth. Additionally, combined therapy with a FAK inhibitor and the antiangiogenic agents pazopanib and bevacizumab reduced tumor growth and inhibited negative effects following withdrawal of antiangiogenic therapy. In summary, these results suggest that FAK may be a unique target in situations in which antiangiogenic agents are withdrawn, and dual targeting of FAK and VEGF could have therapeutic implications for ovarian cancer management.
Authors
Monika Haemmerle, Justin Bottsford-Miller, Sunila Pradeep, Morgan L. Taylor, Hyun-Jin Choi, Jean M. Hansen, Heather J. Dalton, Rebecca L. Stone, Min Soon Cho, Alpa M. Nick, Archana S. Nagaraja, Tony Gutschner, Kshipra M. Gharpure, Lingegowda S. Mangala, Rajesha Rupaimoole, Hee Dong Han, Behrouz Zand, Guillermo N. Armaiz-Pena, Sherry Y. Wu, Chad V. Pecot, Alan R. Burns, Gabriel Lopez-Berestein, Vahid Afshar-Kharghan, Anil K. Sood
Total citations by year
Citation information
Citations to this article (77)
| Title and authors | Publication | Year |
|---|---|---|
|
Mechanisms of Astragalus membranaceus (Fisch.) Bge. var. mongholicus (Bge.) Hsiao (huang qi) and Angelica sinensis (Oliv.) Diels (dang gui) in Ameliorating Hypoxia and Angiogenesis to Delay Pulmonary Nodule Malignant Transformation
Guo Y, Yang P, Wu Z, Zhang S, You F |
Integrative Cancer Therapies | 2025 |
|
Prognostic Significance of Serum Complement Activation, Neutrophil Extracellular Traps and Extracellular DNA in Newly Diagnosed Epithelial Ovarian Cancer
Ricciuti J, Liu Q, Khan AN, Joseph JM, Veuskens BR, Giridharan T, Suzuki S, Emmons TR, Yaffe MB, Kuijpers TW, Jongerius I, Brouwer MC, Pouw RB, Odunsi K, Frederick P, Mager KL, Lele S, Gaulin N, Hakim C, Edwards RP, Olawaiye AB, Sukumanovich P, Taylor S, Elishaev E, Zsiros E, Modugno F, Moysich KB, Segal BH |
Gynecologic oncology | 2025 |
|
Selective apoptosis of tumor-associated platelets boosts the anti-metastatic potency of PD-1 blockade therapy
Wu S, Wu Z, Lu Z, Qi F, Cheng J, Chu T, Li B, Zhao Y, Nie G, Li S |
Cell Reports Medicine | 2025 |
|
Innate Immunity and Platelets: Unveiling Their Role in Chronic Pancreatitis and Pancreatic Cancer
Blümke J, Schameitat M, Verma A, Limbecker C, Arlt E, Kessler SM, Kielstein H, Krug S, Bazwinsky-Wutschke I, Haemmerle M |
Cancers | 2025 |
|
Platelets favor the outgrowth of established metastases
Garcia-Leon MJ, Liboni C, Mittelheisser V, Bochler L, Follain G, Mouriaux C, Busnelli I, Larnicol A, Colin F, Peralta M, Osmani N, Gensbittel V, Bourdon C, Samaniego R, Pichot A, Paul N, Molitor A, Carapito R, Jandrot-Perrus M, Lefebvre O, Mangin PH, Goetz JG |
Nature Communications | 2024 |
|
Angiogenesis-enabled human ovarian tumor microenvironment-chip evaluates pathophysiology of platelets in microcirculation
Ghosh LD, Mathur T, Tronolone JJ, Chuong A, Rangel K, Corvigno S, Sood AK, Jain A |
Advanced Healthcare Materials | 2024 |
|
Revisiting the association between pretreatment thrombocytosis and cancer survival outcomes: an umbrella review of meta-analyses
Shu C, Wang X, Li C, Huang J, Xie X, Li H, Zhao J, Wang Z, He Y, Zhou Y |
BMC Cancer | 2024 |
|
Research progress on platelets in glioma
Zuo M, Li T, Wang Z, Xiang Y, Chen S, Liu Y |
Chinese Medical Journal | 2024 |
|
Interactions between Platelets and Tumor Microenvironment Components in Ovarian Cancer and Their Implications for Treatment and Clinical Outcomes
Oncul S, Cho MS |
Cancers | 2023 |
|
Platelets in the tumor microenvironment and their biological effects on cancer hallmarks
Chen L, Zhu C, Pan F, Chen Y, Xiong L, Li Y, Chu X, Huang G |
Frontiers in Oncology | 2023 |
|
Megakaryocytes respond during sepsis and display innate immune cell behaviors.
Frydman GH, Ellett F, Jorgensen J, Marand AL, Zukerberg L, Selig MK, Tessier SN, Wong KHK, Olaleye D, Vanderburg CR, Fox JG, Tompkins RG, Irimia D |
Frontiers in immunology | 2023 |
|
Nanoparticle-Based Combination Therapy for Ovarian Cancer
Wu Y, Yang Y, Lv X, Gao M, Gong X, Yao Q, Liu Y |
International Journal of Nanomedicine | 2023 |
|
Crosstalk of Immune Cells and Platelets in an Ovarian Cancer Microenvironment and Their Prognostic Significance
Pankowska KA, Będkowska GE, Chociej-Stypułkowska J, Rusak M, Dąbrowska M, Osada J |
International journal of molecular sciences | 2023 |
|
The role of platelets in the regulation of tumor growth and metastasis: the mechanisms and targeted therapy
Liao K, Zhang X, Liu J, Teng F, He Y, Cheng J, Yang Q, Zhang W, Xie Y, Guo D, Cao G, Xu Y, Huang B, Wang X |
2023 | |
|
Focal adhesion kinase: from biological functions to therapeutic strategies
Tan X, Yan Y, Song B, Zhu S, Mei Q, Wu K |
Experimental Hematology and Oncology | 2023 |
|
The prospects of microphysiological systems in modeling platelet pathophysiology in cancer
Ghosh LD, Jain A |
Platelets | 2023 |
|
The dynamic role of platelets in cancer progression and their therapeutic implications.
Li S, Lu Z, Wu S, Chu T, Li B, Qi F, Zhao Y, Nie G |
Nature reviews. Cancer | 2023 |
|
Decoding the role of platelets in tumour metastasis: enigmatic accomplices and intricate targets for anticancer treatments
Zhao J, Huang A, Zeller J, Peter K, McFadyen JD |
Frontiers in immunology | 2023 |
|
Macrophages and platelets in liver fibrosis and hepatocellular carcinoma
Casari M, Siegl D, Deppermann C, Schuppan D |
Frontiers in immunology | 2023 |
|
Revealing profile of cancer-educated platelets and their factors to foster immunotherapy development.
Trivanović D, Mojsilović S, Bogosavljević N, Jurišić V, Jauković A |
Translational oncology | 2023 |
|
Beyond Hemostasis: Platelet Innate Immune Interactions and Thromboinflammation
J Mandel, M Casari, M Stepanyan, A Martyanov, C Deppermann |
International journal of molecular sciences | 2022 |
|
Of vascular defense, hemostasis, cancer, and platelet biology: an evolutionary perspective
D Menter, V Afshar-Kharghan, J Shen, S Martch, A Maitra, S Kopetz, K Honn, A Sood |
Cancer and Metastasis Reviews | 2022 |
|
FAK in Cancer: From Mechanisms to Therapeutic Strategies
H Chuang, Y Zhen, Y Tsai, C Chuang, M Hsiao, M Huang, C Yang |
International journal of molecular sciences | 2022 |
|
Dynamic changes of platelets before and after surgery predict the prognosis of patients with operable non-small cell lung cancer
W Yang, Y Yao, Y Chen, F Jin, T Zheng, X Ai, T Zhang, C Ding, M Jiang |
Journal of Cancer | 2022 |
|
Intratumoral Platelets: Harmful or Incidental Bystanders of the Tumor Microenvironment?
O Chapelain, B Ho-Tin-Noé |
Cancers | 2022 |
|
Biodegradable electrospun nanofibrous platform integrating antiplatelet therapy-chemotherapy for preventing postoperative tumor recurrence and metastasis
J Li, J Li, Y Yao, T Yong, N Bie, Z Wei, X Li, S Li, J Qin, H Jia, Q Du, X Yang, L Gan |
Theranostics | 2022 |
|
Platelets Increase the Expression of PD-L1 in Ovarian Cancer
Cho MS, Lee H, Gonzalez-Delgado R, Li D, Sasano T, Carlos-Alcalde W, Ma Q, Liu J, Sood AK, Afshar-Kharghan V |
Cancers | 2022 |
|
Platelets in the NETworks interweaving inflammation and thrombosis
Wienkamp AK, Erpenbeck L, Rossaint J |
Frontiers in immunology | 2022 |
|
A narrative review for platelets and their RNAs in cancers: New concepts and clinical perspectives
Xiang Y, Xiang P, Zhang L, Li Y, Zhang J |
Medicine | 2022 |
|
Neutrophil interactions with T cells, platelets, endothelial cells, and of course tumor cells
Segal BH, Giridharan T, Suzuki S, Khan AN, Zsiros E, Emmons TR, Yaffe MB, Gankema AA, Hoogeboom M, Goetschalckx I, Matlung HL, Kuijpers TW |
Immunological Reviews | 2022 |
|
Novel markers for liquid biopsies in cancer management: Circulating platelets and extracellular vesicles
Corvigno S, Johnson AM, Wong KK, Cho MS, Afshar-Kharghan V, Menter DG, Sood AK |
Molecular cancer therapeutics | 2022 |
|
Human tumor microenvironment chip evaluates the consequences of platelet extravasation and combinatorial antitumor-antiplatelet therapy in ovarian cancer
B Saha, T Mathur, JJ Tronolone, M Chokshi, GK Lokhande, A Selahi, AK Gaharwar, V Afshar-Kharghan, AK Sood, G Bao, A Jain |
Science Advances | 2021 |
|
Platelet-Cancer Interplay: Molecular Mechanisms and New Therapeutic Avenues
A Braun, HJ Anders, T Gudermann, E Mammadova-Bach |
Frontiers in Oncology | 2021 |
|
Perivascular cell‐derived extracellular vesicles stimulate colorectal cancer revascularization after withdrawal of antiangiogenic drugs
M Huang, M Chen, M Qi, G Ye, J Pan, C Shi, Y Yang, L Zhao, X Mo, Y Zhang, Y Li, J Zhong, W Lu, X Li, J Zhang, J Lin, L Luo, T Liu, PM Tang, A Hong, Y Cao, W Ye, D Zhang |
Journal of Extracellular Vesicles | 2021 |
|
The effect of platelet G proteins on platelet extravasation and tumor growth in the murine model of ovarian cancer
MS Cho, J Li, R Gonzalez-Delgado, H Lee, M Vasquez, T He, Y He, K Liu, T Sasano, B Nürnberg, AK Sood, ST Wong, V Afshar-Kharghan |
Blood Advances | 2021 |
|
A human multi-cellular model shows how platelets drive production of diseased extracellular matrix and tissue invasion
B Malacrida, S Nichols, E Maniati, R Jones, R Delanie-Smith, R Roozitalab, EJ Tyler, M Thomas, G Boot, J Mackerodt, M Lockley, MM Knight, FR Balkwill, OM Pearce |
iScience | 2021 |
|
Platelet transfusion for cancer secondary thrombocytopenia: Platelet and cancer cell interaction
J Wang, P Zhou, Y Han, H Zhang |
Translational oncology | 2021 |
|
Economical and easily detectable markers of digestive tumors: platelet parameters
Yingying Chen, Wei Yang, Lifang Ye, Suzhen Lin, Kuangyi Shu, Xiao Yang, Xinyi Ai, Yating Yao, Minghua Jiang |
Biomarkers in Medicine | 2021 |
|
Platelet CLEC2-Podoplanin Axis as a Promising Target for Oral Cancer Treatment
B Hwang, S Park, E Cho, X Zhang, S Lee, H Ahn, K Chun, W Chung, N Song |
Frontiers in immunology | 2021 |
|
Analysis of risk factors and gene mutation characteristics of different metastatic sites of lung cancer
B Wang, S Chen, H Xiao, J Zhang, D Liang, J Shan, H Zou |
Cancer Medicine | 2021 |
|
OvCa-Chip microsystem recreates vascular endothelium–mediated platelet extravasation in ovarian cancer
B Saha, T Mathur, KF Handley, W Hu, V Afshar-Kharghan, AK Sood, A Jain |
Blood Advances | 2020 |
|
Multifaceted Functions of Platelets in Cancer: From Tumorigenesis to Liquid Biopsy Tool and Drug Delivery System
M Dovizio, P Ballerini, R Fullone, S Tacconelli, A Contursi, P Patrignani |
International journal of molecular sciences | 2020 |
|
Platelets and Metastasis: New Implications of an Old Interplay
S Lucotti, RJ Muschel |
Frontiers in Oncology | 2020 |
|
Platelet-Leukocyte Interplay in Cancer Development and Progression
D Stoiber, A Assinger |
Cells | 2020 |
|
Podoplanin promotes cancer-associated thrombosis and contributes to the unfavorable overall survival in an ectopic xenograft mouse model of oral cancer
HY Lee, NY Yu, SH Lee, HJ Tsai, CC Wu, JC Cheng, DP Chen, YR Wang, CP Tseng |
Biomedical journal | 2020 |
|
Platelets, Thrombocytosis, and Ovarian Cancer Prognosis: Surveying the Landscape of the Literature
DH Hufnagel, GD Cozzi, MA Crispens, A Beeghly-Fadiel |
International journal of molecular sciences | 2020 |
|
Blood platelets stimulate cancer extravasation through TGFβ-mediated downregulation of PRH/HHEX
E Marcolino, YH Siddiqui, M van den Bosch, AW Poole, PS Jayaraman, K Gaston |
Oncogenesis | 2020 |
|
Paclitaxel, Carboplatin, and Bevacizumab in Advanced Cervical Cancer: A Treatment Response and Safety Analysis
W Tao, J Yang, Y Jiang, W Chen, Y Wang |
Dose-Response | 2020 |
|
Hypoxia-Mediated Decrease of Ovarian Cancer Cells Reaction to Treatment: Significance for Chemo- and Immunotherapies
A Klemba, L Bodnar, H Was, KK Brodaczewska, G Wcislo, CA Szczylik, C Kieda |
International journal of molecular sciences | 2020 |
|
Mechanisms and biomarkers of cancer-associated thrombosis
AS Kim, AA Khorana, KR McCrae |
Translational research : the journal of laboratory and clinical medicine | 2020 |
|
A Phase I Open‐Label Clinical Trial Evaluating the Therapeutic Vaccine hVEGF26 –104/ RFASE in Patients with Advanced Solid Malignancies
RS Goedegebuure, MQ Wentink, HJ Vliet, P Timmerman, AW Griffioen, TD Gruijl, HM Verheul |
The oncologist | 2020 |
|
Patrolling the vascular borders: platelets in immunity to infection and cancer
F Gaertner, S Massberg |
Nature Reviews Immunology | 2019 |
|
Tumor angiogenesis: causes, consequences, challenges and opportunities
R Lugano, M Ramachandran, A Dimberg |
Cellular and Molecular Life Sciences | 2019 |
|
Role of Focal Adhesion Kinase in Small-Cell Lung Cancer and Its Potential as a Therapeutic Target
FA Nana, M Vanderputten, S Ocak |
Cancers | 2019 |
|
Targeting Angiogenesis With Peptide Vaccines
MA Rahat |
Frontiers in immunology | 2019 |
|
Novel Aspects of Extracellular Vesicles as Mediators of Cancer-Associated Thrombosis
VH Almeida, AM Rondon, T Gomes, RQ Monteiro |
Cells | 2019 |
|
FAK activity sustains intrinsic and acquired ovarian cancer resistance to platinum chemotherapy
CJ Osterman, D Ozmadenci, EG Kleinschmidt, KN Taylor, AM Barrie, S Jiang, LM Bean, FJ Sulzmaier, C Jean, I Tancioni, K Anderson, S Uryu, EA Cordasco, J Li, XL Chen, G Fu, M Ojalill, P Rappu, J Heino, AM Mark, G Xu, KM Fisch, VN Kolev, DT Weaver, JA Pachter, B Győrffy, MT McHale, DC Connolly, A Molinolo, DG Stupack, DD Schlaepfer |
eLife | 2019 |
|
Increased Expression and Activation of FAK in Small-Cell Lung Cancer Compared to Non-Small-Cell Lung Cancer
FA Nana, D Hoton, J Ambroise, M Lecocq, M Vanderputten, Y Sibille, B Vanaudenaerde, C Pilette, C Bouzin, S Ocak |
Cancers | 2019 |
|
Impacts of Cancer on Platelet Production, Activation and Education and Mechanisms of Cancer-Associated Thrombosis
L Plantureux, D Mège, L Crescence, F Dignat-George, C Dubois, L Panicot-Dubois |
Cancers | 2018 |
|
The Platelet Lifeline to Cancer: Challenges and Opportunities
M Haemmerle, RL Stone, DG Menter, V Afshar-Kharghan, AK Sood |
Cancer Cell | 2018 |
|
Advances in Clinical and Basic Science of Coagulation: Illustrated abstracts of the 9th Chapel Hill Symposium on Hemostasis
W Bergmeier, S Antoniak, EM Conway, CV Denis, LA George, B Isermann, NS Key, S Krishnaswamy, WA Lam, D Lillicrap, J Liu, MR Looney, JA López, C Maas, F Peyvandi, W Ruf, AK Sood, HH Versteeg, AS Wolberg, PC Wong, JP Wood, H Weiler |
Research and Practice in Thrombosis and Haemostasis | 2018 |
|
Mitochondrial DNA in the tumour microenvironment activates neutrophils and is associated with worse outcomes in patients with advanced epithelial ovarian cancer
KL Singel, KS Grzankowski, AN Khan, MJ Grimm, AC DAuria, K Morrell, KH Eng, B Hylander, PC Mayor, TR Emmons, N Lénárt, R Fekete, Z Környei, U Muthukrishnan, JD Gilthorpe, CF Urban, K Itagaki, CJ Hauser, C Leifer, KB Moysich, K Odunsi, Á Dénes, BH Segal |
British Journal of Cancer | 2018 |
|
The FAK inhibitor BI 853520 inhibits spheroid formation and orthotopic tumor growth in malignant pleural mesothelioma
V Laszlo, Z Valko, J Ozsvar, I Kovacs, T Garay, MA Hoda, T Klikovits, P Stockhammer, C Aigner, M Gröger, W Klepetko, W Berger, M Grusch, J Tovari, IC Waizenegger, B Dome, B Hegedus |
Journal of Molecular Medicine | 2018 |
|
Platelets reduce anoikis and promote metastasis by activating YAP1 signaling
M Haemmerle, ML Taylor, T Gutschner, S Pradeep, MS Cho, J Sheng, YM Lyons, AS Nagaraja, RL Dood, Y Wen, LS Mangala, JM Hansen, R Rupaimoole, KM Gharpure, C Rodriguez-Aguayo, SY Yim, JS Lee, C Ivan, W Hu, G Lopez-Berestein, ST Wong, BY Karlan, DA Levine, J Liu, V Afshar-Kharghan, AK Sood |
Nature Communications | 2017 |
|
Role of ADP receptors on platelets in the growth of ovarian cancer
MS Cho, K Noh, M Haemmerle, D Li, H Park, Q Hu, T Hisamatsu, T Mitamura, SL Mak, S Kunapuli, Q Ma, AK Sood, V Afshar-Kharghan |
Blood | 2017 |
|
Role of Platelet-Derived Tgfβ1 in the Progression of Ovarian Cancer
Q Hu, T Hisamatsu, M Haemmerle, MS Cho, S Pradeep, R Rupaimoole, C Rodriguez-Aguayo, G Lopez-Berestein, ST Wong, AK Sood, V Afshar-Kharghan |
Clinical cancer research | 2017 |
|
Podoplanin enhances lung cancer cell growth in vivo by inducing platelet aggregation
K Miyata, A Takemoto, S Okumura, M Nishio, N Fujita |
Scientific Reports | 2017 |
|
Targeting Platelets for the Treatment of Cancer
O Elaskalani, M Berndt, M Falasca, P Metharom |
Cancers | 2017 |
|
Maintenance of antiangiogenic and antitumor effects by orally active low-dose capecitabine for long-term cancer therapy
Y Zhang, M Sun, G Huang, L Yin, Q Lai, Y Yang, X Xing, G Yu, Y Sun, X Wang, G Nie, Y Liu, Y Cao |
Proceedings of the National Academy of Sciences | 2017 |
|
Platelet “first responders” in wound response, cancer, and metastasis
DG Menter, S Kopetz, E Hawk, AK Sood, JM Loree, P Gresele, KV Honn |
Cancer and Metastasis Reviews | 2017 |
|
Diabetic concentrations of metformin inhibit platelet-mediated ovarian cancer cell progression
R Erices, S Cubillos, R Aravena, F Santoro, M Marquez, R Orellana, C Ramírez, P González, P Fuenzalida, ML Bravo, B Oliva, S Kato, C Ibañez, J Brañes, E Bravo, C Alonso, K García, C Arab, VA Torres, AS Godoy, J Pereira, G Bustos, JC Cardenas, MA Cuello, GI Owen |
Oncotarget | 2017 |
|
Recent Advances in Understanding, Diagnosing, and Treating Ovarian Cancer
K Mills, K Fuh |
F1000Research | 2017 |
|
miR-135a inhibits tumor metastasis and angiogenesis by targeting FAK pathway
Z Cheng, F Liu, H Zhang, X Li, Y Li, J Li, F Liu, Y Cao, L Cao, F Li |
Oncotarget | 2017 |
|
Bevacizumab for recurrent, persistent or advanced cervical cancer: reproducibility of GOG 240 study results in “real world” patients
A Godoy-Ortiz, Y Plata, J Alcaide, A Galeote, B Pajares, E Saez, E Alba, A Sánchez-Muñoz |
Clinical and Translational Oncology | 2017 |
|
From tumorigenesis to microenvironment and immunoregulation: the many faces of focal adhesion kinase and challenges associated with targeting this elusive protein
FL Lenzo, WG Cance |
Translational cancer research | 2017 |
|
Anti-tumor and Anti-angiogenic Effects of Aspirin-PC in Ovarian Cancer
Y Huang, LM Lichtenberger, M Taylor, JN Bottsford-Miller, M Haemmerle, MJ Wagner, Y Lyons, S Pradeep, W Hu, RA Previs, JM Hansen, D Fang, PL Domiak, J Filant, EJ Dial, F Shen, H Hatakeyama, AK Sood |
Molecular cancer therapeutics | 2016 |
|
Precision targeted therapy of ovarian cancer
J Sapiezynski, O Taratula, L Rodriguez-Rodriguez, T Minko |
Journal of Controlled Release | 2016 |
Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)