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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
November 14, 2017

Anti-angiogenesis therapy has shown clinical benefit in patients with high-grade 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 pro-angiogenic 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 anti-angiogenesis 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

November 14, 2017

Volume

8

Issue

57

Start / End Page

96496 / 96505

Location

United States

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, Yasmin A., Sunila Pradeep, Sherry Y. Wu, Monika Haemmerle, Jean M. Hansen, Michael J. Wagner, Alejandro 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 (November 14, 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 Nov 14;8(57):96496–505.
Lyons, Yasmin 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, Nov. 2017, pp. 96496–505. Pubmed, 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 Nov 14;8(57):96496–96505.

Published In

Oncotarget

DOI

EISSN

1949-2553

Publication Date

November 14, 2017

Volume

8

Issue

57

Start / End Page

96496 / 96505

Location

United States

Related Subject Headings

  • 3211 Oncology and carcinogenesis
  • 1112 Oncology and Carcinogenesis