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Maintenance of antiangiogenic and antitumor effects by orally active low-dose capecitabine for long-term cancer therapy.

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journal contribution
posted on 2019-09-24, 15:33 authored by 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
Long-term uninterrupted therapy is essential for maximizing clinical benefits of antiangiogenic drugs (AADs) in cancer patients. Unfortunately, nearly all clinically available AADs are delivered to cancer patients using disrupted regimens. We aim to develop lifetime, nontoxic, effective, orally active, and low-cost antiangiogenic and antitumor drugs for treatment of cancer patients. Here we report our findings of long-term maintenance therapy with orally active, nontoxic, low cost antiangiogenic chemotherapeutics for effective cancer treatment. In a sequential treatment regimen, robust antiangiogenic effects in tumors were achieved with an anti-VEGF drug, followed by a low-dose chemotherapy. The nontoxic, low dose of the orally active prodrug capecitabine was able to sustain the anti-VEGF-induced vessel regression for long periods. In another experimental setting, maintenance of low-dose capecitabine produced greater antiangiogenic and antitumor effects after AAD plus chemotherapy. No obvious adverse effects were developed after more than 2-mo of consecutive treatment with a low dose of capecitabine. Together, our findings provide a rationalized concept of effective cancer therapy by long-term maintenance of AAD-triggered antiangiogenic effects with orally active, nontoxic, low-cost, clinically available chemotherapeutics.

Funding

The Y.C. laboratory is supported through research grants from the European Research Council Advanced Grant ANGIOFAT (Project no. 250021); the Swedish Research Council; the Swedish Cancer Foundation; the Children Cancer Foundation; the Diabetes Foundation; the Karolinska Institute Foundation; the Karolinska Institute Distinguished Professor Award; the Torsten Soderbergs Foundation; the Maud and Birger Gustavsson Foundation; the NOVO Nordisk Foundation; and the Knut and Alice Wallenberg Foundation. Guohui Nie is supported by Fund for High Level University Construction of Medical Discipline (2016031638), China and The Shenzhen Science and Technology Innovation Committee (JCYJ20150403091443336).

History

Citation

Proceedings of the National Academy of Sciences (PNAS), 2017, 114 (26), pp. E5226-E5235

Author affiliation

/Organisation/COLLEGE OF LIFE SCIENCES/School of Medicine/Department of Cardiovascular Sciences

Version

  • VoR (Version of Record)

Published in

Proceedings of the National Academy of Sciences (PNAS)

Publisher

National Academy of Sciences

eissn

1091-6490

Acceptance date

2017-05-15

Copyright date

2017

Available date

2019-09-24

Publisher version

https://www.pnas.org/content/114/26/E5226

Notes

This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1705066114/-/DCSupplemental.

Language

en