Anti-VEGF Therapies in the Clinic

Meadows, Kellen L.; Hurwitz, Herbert I.

doi:10.1101/cshperspect.a006577

Cited by 202 publications

(128 citation statements)

References 124 publications

(117 reference statements)

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“…In summary, there are at least 12 VEGF/VEGFR inhibitors that are approved, and many more in clinical trials; none have a biomarker for patient selection (34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44). Yet, it is known that most of these agents improve survival by only a few weeks, most likely because a subset of patients respond, whereas others do not benefit or may even be harmed by these drugs.…”

Section: Discussionmentioning

confidence: 99%

TP53Alterations Correlate with Response to VEGF/VEGFR Inhibitors: Implications for Targeted Therapeutics

Wheler

Janků

Naing

et al. 2016

Molecular Cancer Therapeutics

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Section: Discussionmentioning

confidence: 99%

TP53Alterations Correlate with Response to VEGF/VEGFR Inhibitors: Implications for Targeted Therapeutics

Wheler

Janků

Naing

et al. 2016

Molecular Cancer Therapeutics

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“…Currently, angiogenesis is acknowledged as a key and validated cancer therapeutic target due to its pivotal role in the progression and metastasis of malignancies (26,27). Worldwide, gastric cancer is one of the leading causes of cancer-associated mortality (2).…”

Section: Discussionmentioning

confidence: 99%

Interleukin-8: A potent promoter of angiogenesis in gastric cancer

Shi

Wei

2015

Oncology Letters

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“…4,5 Anti-angiogenic therapies, mostly targeting the VEGF/VEGFR signaling axis, are currently routinely used in the clinic to treat several advanced or metastatic cancers, including colon, kidney, liver and breast cancers. [6][7][8] However, survival benefits are limited and experimental evidence indicates that resistance mechanisms to anti-angiogenic therapy are responsible for its weak therapeutic efficacy. [9][10][11] The tumor stroma itself can confer resistance to anti-angiogenic therapy.…”

Section: Introductionmentioning

confidence: 99%

Arginase inhibition suppresses lung metastasis in the 4T1 breast cancer model independently of the immunomodulatory and anti-metastatic effects of VEGFR-2 blockade

et al. 2017

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Tumor angiogenesis promotes tumor growth and metastasis. Anti-angiogenic therapy in combination with chemotherapy is used for the treatment of metastatic cancers, including breast cancer but therapeutic benefits are limited. Mobilization and accumulation of myeloid-derived suppressor cells (MDSC) during tumor progression and therapy have been implicated in metastasis formation and resistance to antiangiogenic treatments. Here, we used the 4T1 orthotopic syngenic mouse model of mammary adenocarcinoma to investigate the effect of VEGF/VEGFR-2 axis inhibition on lung metastasis, MDSC and regulatory T cells (Tregs). We show that treatment with the anti-VEGFR-2 blocking antibody DC101 inhibits primary tumor growth, angiogenesis and lung metastasis. DC101 treatment had no effect on MDSC mobilization, but partially attenuated the inhibitory effect of mMDSC on T cell proliferation and decreased the frequency of Tregs in primary tumors and lung metastases. Strikingly, DC101 treatment induced the expression of the immune-suppressive molecule arginase I in mMDSC. Treatment with the arginase inhibitor N v -hydroxy-nor-Arginine (Nor-NOHA) reduced the inhibitory effect of MDSC on T cell proliferation and inhibited number and size of lung metastasis but had little or no additional effects in combination with DC101.In conclusion, DC101 treatment suppresses 4T1 tumor growth and metastasis, partially reverses the inhibitory effect of mMDSC on T cell proliferation, decreases Tregs in tumors and increases arginase I expression in mMDSC. Arginase inhibition suppresses lung metastasis independently of DC101 effects. These observations contribute to the further characterization of the immunomodulatory effect of anti-VEGF/VEGFR2 therapy and provide a rationale to pursue arginase inhibition as potential anti-metastatic therapy.

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Anti-VEGF Therapies in the Clinic

Cited by 202 publications

References 124 publications

TP53Alterations Correlate with Response to VEGF/VEGFR Inhibitors: Implications for Targeted Therapeutics

TP53Alterations Correlate with Response to VEGF/VEGFR Inhibitors: Implications for Targeted Therapeutics

Interleukin-8: A potent promoter of angiogenesis in gastric cancer

Arginase inhibition suppresses lung metastasis in the 4T1 breast cancer model independently of the immunomodulatory and anti-metastatic effects of VEGFR-2 blockade

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