Systems pharmacology approaches for optimization of antiangiogenic therapies: challenges and opportunities

Frontiers in Pharmacology
S Sharan, S Woo

Abstract

Targeted therapies have become an important therapeutic paradigm for multiple malignancies. The rapid development of resistance to these therapies impedes the successful management of advanced cancer. Due to the redundancy in angiogenic signaling, alternative proangiogenic factors are activated upon treatment with anti-VEGF agents. Higher doses of the agents lead to greater stimulation of compensatory proangiogenic pathways that limit the therapeutic efficacy of VEGF-targeted drugs and produce escape mechanisms for tumor. Evidence suggests that dose intensity and schedules affect the dynamics of the development of this resistance. Thus, an optimal dosing regimen is crucial to maximizing the therapeutic benefit of antiangiogenic agents and limiting treatment resistance. A systems pharmacology approach using multiscale computational modeling can facilitate a mechanistic understanding of these dynamics of angiogenic biomarkers and their impacts on tumor reduction and resistance. Herein, we discuss a systems pharmacology approach integrating the biology of VEGF-targeted therapy resistance, including circulating biomarkers, and pharmacodynamics to enable the optimization of antiangiogenic therapy for therapeutic gains.

References

Dec 22, 1983·Proceedings of the Royal Society of London. Series B, Containing Papers of a Biological Character·J W Black, P Leff
Sep 15, 2001·Clinical Pharmacology and Therapeutics·D E Mager, W J Jusko
Mar 21, 2002·Nature Reviews. Cancer·Adrian L Harris
Dec 31, 2002·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Fairooz KabbinavarEmily Bergsland
Apr 16, 2003·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Donald E MagerWilliam J Jusko
Jun 6, 2003·Nature·Donald P Bottaro, Lance A Liotta
Mar 3, 2004·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Michael B AtkinsMatthew L Sherman
Jul 9, 2004·Journal of the National Cancer Institute·Wendy R Parulekar, Elizabeth A Eisenhauer
Aug 18, 2004·Genes & Development·Deirdre A NelsonEileen White
Dec 17, 2004·Pharmacological Reviews·Ann HoebenErnst A De Bruijn
Jul 14, 2006·Nature Reviews. Cancer·Adrian M JubbHartmut Koeppen
Feb 27, 2007·Oncogene·T Pawson, N Warner
Oct 19, 2007·Proceedings of the National Academy of Sciences of the United States of America·John M L EbosRobert S Kerbel
Mar 12, 2008·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Stefan Sleijfer, Erik Wiemer
Apr 5, 2008·Clinical Pharmacology and Therapeutics·D E Mager, W J Jusko
Aug 2, 2008·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Stephen A Cannistra
Aug 2, 2008·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Nilofer S AzadElise C Kohn
Feb 21, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Nilofer S AzadHeidi H Kong
May 14, 2009·Journal of the National Cancer Institute·Christophe Le TourneauLillian L Siu
Jun 2, 2009·Nature Reviews. Clinical Oncology·Rakesh K JainA Gregory Sorensen
Aug 13, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·John M L EbosRobert S Kerbel
Oct 29, 2009·Carcinogenesis·Pamela K Kreeger, Douglas A Lauffenburger
Dec 17, 2009·British Journal of Cancer·N MurukeshG C Jayson
Feb 11, 2010·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Rajul K JainRazelle Kurzrock
Apr 9, 2010·Clinical Pharmacology and Therapeutics·A LindauerU Jaehde
Jun 10, 2010·Clinical Pharmacology and Therapeutics·S R B Allerheiligen
Oct 12, 2010·Nature Medicine·Robert S Kerbel, John M L Ebos
Mar 26, 2011·The Journal of Clinical Investigation·Oriol Casanovas
May 14, 2011·Molecular Aspects of Medicine·Sònia TuguesLena Claesson-Welsh
Jun 30, 2011·The Biochemical Journal·Sina KochLena Claesson-Welsh
Nov 23, 2011·BMC Systems Biology·Stacey D FinleyAleksander S Popel
Feb 7, 2012·Proceedings of the National Academy of Sciences of the United States of America·Sarah J ConleyMax S Wicha
Mar 24, 2012·Science Translational Medicine·Ravi IyengarJames M Gallo
Apr 5, 2012·Genes & Development·Jeremy S Logue, Deborah K Morrison

❮ Previous
Next ❯

Citations

Jan 20, 2016·CPT: Pharmacometrics & Systems Pharmacology·S D FinleyA S Popel
Jun 2, 2015·Oncogenesis·R N Gacche
Oct 21, 2016·Computational and Structural Biotechnology Journal·V R Knight-SchrijverN Le Novère
Jul 8, 2016·Annals of Biomedical Engineering·Thomas E YankeelovGuy M Genin
Jan 1, 2016·NPJ Systems Biology and Applications·Jennifer A RohrsStacey D Finley
May 30, 2020·International Journal of Molecular Sciences·Apostolos PapachristosGregory Sivolapenko

❮ Previous
Next ❯

Methods Mentioned

BETA
xenograft
imaging techniques

Related Concepts

Related Feeds

Angiogenesis Inhibitors to Treat Cancer

Cancer treatments including angiogenesis inhibitors prevent tumor cells from receiving nutrients and oxygen. Here is the latest research on angiogenesis inhibitors for the treatment of cancer.

Arterial-Venous in Development & Disease

Arterial-venous development may play a crucial role in cardiovascular diseases. Here is the latest research.

Related Papers

Frontiers in Bioscience (Elite Edition)
Yutaka Takahashi, Kenji Nishioka
Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Lee M Ellis, Daniel J Hicklin
Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
Amir Abdollahi, Judah Folkman
© 2022 Meta ULC. All rights reserved