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Macrophage depletion through colony stimulating factor 1 receptor pathway blockade overcomes adaptive resistance to anti-VEGF therapy

Publication ,  Journal Article
Lyons, YA; Pradeep, S; Wu, SY; Haemmerle, M; Hansen, JM; Wagner, MJ; Villar-Prados, A; Nagaraja, AS; Dood, RL; Previs, RA; Hu, W; Zhao, Y ...
Published in: Oncotarget
January 1, 2017

Anti-angiogenesis therapy has shown clinical benefit in patients with highgrade serous ovarian cancer (HGSC), but adaptive resistance rapidly emerges. Thus, approaches to overcome such resistance are needed. We developed the setting of adaptive resistance to anti-VEGF therapy, and performed a series of in vivo experiments in both immune competent and nude mouse models. Given the proangiogenic properties of tumor-associated macrophages (TAMs) and the dominant role of CSF1R in macrophage function, we added CSF1R inhibitors following emergence of adaptive resistance to anti-VEGF antibody. Mice treated with a CSF1R inhibitor (AC708) after anti-VEGF antibody resistance had little to no measurable tumor burden upon completion of the experiment while those that did not receive a CSF1R inhibitor still had abundant tumor. To mimic clinically used regimens, mice were also treated with anti-VEGF antibody and paclitaxel until resistance emerged, and then a CSF1R inhibitor was added. The addition of a CSF1R inhibitor restored response to antiangiogenesis therapy, resulting in 83% lower tumor burden compared to treatment with anti-VEGF antibody and paclitaxel alone. Collectively, our data demonstrate that the addition of a CSF1R inhibitor to anti-VEGF therapy and taxane chemotherapy results in robust anti-tumor effects.

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Published In

Oncotarget

DOI

EISSN

1949-2553

Publication Date

January 1, 2017

Volume

8

Issue

57

Start / End Page

96496 / 96505

Related Subject Headings

  • 3211 Oncology and carcinogenesis
  • 1112 Oncology and Carcinogenesis
 

Citation

APA
Chicago
ICMJE
MLA
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Lyons, Y. A., Pradeep, S., Wu, S. Y., Haemmerle, M., Hansen, J. M., Wagner, M. J., … Sood, A. K. (2017). Macrophage depletion through colony stimulating factor 1 receptor pathway blockade overcomes adaptive resistance to anti-VEGF therapy. Oncotarget, 8(57), 96496–96505. https://doi.org/10.18632/oncotarget.20410
Lyons, Y. A., S. Pradeep, S. Y. Wu, M. Haemmerle, J. M. Hansen, M. J. Wagner, A. Villar-Prados, et al. “Macrophage depletion through colony stimulating factor 1 receptor pathway blockade overcomes adaptive resistance to anti-VEGF therapy.” Oncotarget 8, no. 57 (January 1, 2017): 96496–505. https://doi.org/10.18632/oncotarget.20410.
Lyons YA, Pradeep S, Wu SY, Haemmerle M, Hansen JM, Wagner MJ, et al. Macrophage depletion through colony stimulating factor 1 receptor pathway blockade overcomes adaptive resistance to anti-VEGF therapy. Oncotarget. 2017 Jan 1;8(57):96496–505.
Lyons, Y. A., et al. “Macrophage depletion through colony stimulating factor 1 receptor pathway blockade overcomes adaptive resistance to anti-VEGF therapy.” Oncotarget, vol. 8, no. 57, Jan. 2017, pp. 96496–505. Scopus, doi:10.18632/oncotarget.20410.
Lyons YA, Pradeep S, Wu SY, Haemmerle M, Hansen JM, Wagner MJ, Villar-Prados A, Nagaraja AS, Dood RL, Previs RA, Hu W, Zhao Y, Mak DH, Xiao Z, Melendez BD, Lizee GA, Mercado-Uribe I, Baggerly KA, Hwu P, Liu J, Overwijk WW, Coleman RL, Sood AK. Macrophage depletion through colony stimulating factor 1 receptor pathway blockade overcomes adaptive resistance to anti-VEGF therapy. Oncotarget. 2017 Jan 1;8(57):96496–96505.

Published In

Oncotarget

DOI

EISSN

1949-2553

Publication Date

January 1, 2017

Volume

8

Issue

57

Start / End Page

96496 / 96505

Related Subject Headings

  • 3211 Oncology and carcinogenesis
  • 1112 Oncology and Carcinogenesis