Efficacy and safety of bevacizumab in combination with docetaxel for the first-line treatment of elderly patients with locally recurrent or metastatic breast cancer: Results from AVADO

Pivot, Xavier; Schneeweiß, Andreas; Verma, Shailendra; Thomssen, Christoph; Passos‐Coelho, José Luís; Benedetti, Giovanni; Ciruelos, Eva; Moos, Roger von; Chang, Hong‐Tai; Duenne, Anja-Alexandra; Miles, David

doi:10.1016/j.ejca.2011.06.018

Cited by 97 publications

(59 citation statements)

References 33 publications

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“…The approval of inhibitors of angiogenesis has been limited because after an initial prolongation of progression-free survival and improved patient response rates, they do not always translate into better overall survival, thus casting doubt on the overall efficacy of antiangiogenic therapy (4)(5)(6). Resistance to antiangiogenic therapy has also been reported both in preclinical and clinical studies often associated with the activation of alternative proangiogenic pathways (7,8).…”

Section: Introductionmentioning

confidence: 99%

Chemotherapy Counteracts Metastatic Dissemination Induced by Antiangiogenic Treatment in Mice

Rovida

Castiglioni

Decio

et al. 2013

Molecular Cancer Therapeutics

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The development of resistance and progressive disease after treatment with angiogenesis inhibitors is becoming a controversial issue. We investigated the experimental conditions that cause multireceptor tyrosine kinase inhibitors (RTKI) to augment metastasis and whether opportune combinations with chemotherapy could counteract this effect. The renal Renca-luc tumor was transplanted orthotopically in the kidney of Balb/c mice, which then were or were not nephrectomized. The Lewis Lung carcinoma (LLC) was transplanted in the tibial muscle of C57/Bl6 mice. Treatment with the RTKI sunitinib started at different stages of tumor progression, mimicking neoadjuvant or adjuvant settings. Combination studies with paclitaxel, doxorubicin, cisplatin, gemcitabine, and topotecan were done on the LLC model, using opportune regimens. In a neoadjuvant setting, sunitinib inhibited Renca-luc tumor growth, prolonging survival despite an increase in lung metastasis; treatment after primary tumor surgery (adjuvant setting) or on established metastasis prolonged survival and decreased metastasis. Sunitinib increased lung metastasis from mice bearing early-stage LLC, but did not affect established metastases (no acceleration) from advanced tumors. Combinations with doxorubicin, topotecan, gemcitabine, but not cisplatin and paclitaxel, counteracted the increase in metastasis from LLC, partly reflecting their antitumor activity. Histology analysis after sunitinib confirmed tumor vascular changes and increased hypoxia. Topotecan at suboptimal daily doses reduced sunitinib-related metastasis, reducing tumor hypoxia. Tyrosine kinase inhibitors, as sunitinib, can have adverse malignant effects mainly in the neoadjuvant setting. The addition of chemotherapy might influence metastasis, depending on each drug mechanism of action and its regimen of administration.

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Section: Introductionmentioning

confidence: 99%

Chemotherapy Counteracts Metastatic Dissemination Induced by Antiangiogenic Treatment in Mice

Rovida

Castiglioni

Decio

et al. 2013

Molecular Cancer Therapeutics

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“…As firstline therapy widely used for various types of cancer in the clinic, chemotherapy is suitable for the therapeutic elements of theranostics. Applying existing treatment regimens and following existing safety guidelines for chemotherapy can provide proven therapeutic elements to these techniques [8,9]. However, chemotherapy has several limitations associated with its use.…”

Section: Methods and Resultsmentioning

confidence: 99%

Polymer Nanoassemblies With solvato- and halo-fluorochromism for Drug Release Monitoring and Metastasis Imaging

2015

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Background: Theranostics, an emerging technique that combines therapeutic and diagnostic modalities for various diseases, holds promise to detect cancer in early stages, eradicate metastatic tumors and ultimately reduce cancer mortality. Methods & results:This study reports unique polymer nanoassemblies that increase fluorescence intensity upon addition of hydrophobic drugs and either increase or decrease fluorescence intensity in acidic environments, depending on nanoparticle core environment properties. Extensive spectroscopic analyses were performed to determine optimal excitation and emission wavelengths, which enabled real time measurement of drugs releasing from the nanoassemblies and ex vivo imaging of acidic liver metastatic tumors from mice. Conclusion: Polymer nanoassemblies with solvato-and halo-fluorochromic properties are promising platforms to develop novel theranostic tools for the detection and treatment of metastatic tumors.

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“…These results suggest that ARHGAP17 mediated by VEGF–NRP1 interaction partly contributed to DFS in HR(−) BCs. As shown in Supporting Information Table S10, the association between HR status and bevacizumab treatment efficacy in clinical trials has been inconsistent 9, 41, 42, 43, 44, 45, 46, 47. Our findings demonstrated that there are bevacizumab‐independent VEGF signals in HR(−) BC tumors.…”

Section: Discussionmentioning

confidence: 61%

Long isoform of VEGF stimulates cell migration of breast cancer by filopodia formation via NRP1/ARHGAP17/Cdc42 regulatory network

Kiso

Tanaka

Toi

et al. 2018

Intl Journal of Cancer

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VEGF stimulates endothelial cells as a key molecule in angiogenesis. VEGF also works as a multifunction molecule, which targets a variety of cell members in the tumor microenvironment. We aimed to reveal VEGF‐related molecular mechanisms on breast cancer cells. VEGF‐knocked‐out MDA‐MB‐231 cells (231VEGFKOex3) showed rounded morphology and shorter perimeter (1.6‐fold, p < 0.0001). The 231VEGFKOex3 cells also showed impaired cell migration (2.6‐fold, p = 0.002). Bevacizumab treatment did not induce any change in morphology and mobility. Soluble neuropilin‐1 overexpressing MDA‐MB‐231 cells (231sNRP1) exhibited rounded morphology and shorter perimeter (1.3‐fold, p < 0.0001). The 231sNRP1 cells also showed impaired cell migration (1.7‐fold, p = 0.003). These changes were similar to that of 231VEGFKOex3 cells. As MDA‐MB‐231 cells express almost no VEGFR, these results indicate that the interaction between NRP1 and long isoform of VEGF containing a NRP‐binding domain regulates the morphology and migration ability of MDA‐MB‐231 cells. Genome‐wide gene expression profiling identified ARHGAP17 as one of the target genes in the downstream of the VEGF/NRP1 signal. We also show that VEGF/NRP1 signal controls filopodia formation of the cells by modulating Cdc42 activity via ARHGAP17. Among 1,980 breast cancer cases from a public database, the ratio of VEGF and SEMA3A in primary tumors (n = 450) of hormone‐receptor‐negative breast cancer is associated with ARHGAP17 expression inversely, and with disease free survival. Altogether, the bevacizumab‐independent VEGF/NRP1/ARHGAP17/Cdc42 regulatory network plays important roles in malignant behavior of breast cancer.

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Efficacy and safety of bevacizumab in combination with docetaxel for the first-line treatment of elderly patients with locally recurrent or metastatic breast cancer: Results from AVADO

Cited by 97 publications

References 33 publications

Chemotherapy Counteracts Metastatic Dissemination Induced by Antiangiogenic Treatment in Mice

Chemotherapy Counteracts Metastatic Dissemination Induced by Antiangiogenic Treatment in Mice

Polymer Nanoassemblies With solvato- and halo-fluorochromism for Drug Release Monitoring and Metastasis Imaging

Long isoform of VEGF stimulates cell migration of breast cancer by filopodia formation via NRP1/ARHGAP17/Cdc42 regulatory network

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