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Updated: May 17, 2026

Evaluating the Effectiveness of Cancer Drug Sensitization In Vitro and In Vivo
Published on: February 6, 2015
Assessing the in vivo efficacy of biologic antiangiogenic therapies
Peter M Wilson1, Melissa J LaBonte, Heinz-Josef Lenz
1Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. pmwilson@usc.edu
Purpose:
To review key clinical issues underlying the assessment of in vivo efficacy when using antiangiogenic therapies for cancer treatment.
Methods:
Literature relevant to use of antiangiogenic therapies in cancer was reviewed, with particular emphasis on the assessment of in vivo efficacy of these agents, as well as additional angiogenic factors that could play a role in escape from angiogenesis inhibition.
Results:
In order to grow and metastasize, tumors need to continually acquire new blood supplies; therefore, therapeutic inhibition of angiogenesis has become a component of anticancer treatment for many tumor types. Bevacizumab, a humanized monoclonal antibody directed at vascular endothelial growth factor A (VEGF-A), has shown activity in combination with chemotherapy in metastatic colorectal cancer. Nevertheless, the use of antiangiogenic therapies remains suboptimal; specifically, optimal dose, duration of therapy, and combination of agents remain unknown. Also, at present, it is not possible to determine which patients are most likely to respond to a given form of antiangiogenic therapy. There has been increased recognition of alternative pathways possibly associated with disease progression in patients undergoing antiangiogenic therapy targeted at VEGF-A. Multiligand-targeted antiangiogenic therapies, such as ziv-aflibercept (formerly known as aflibercept, VEGF Trap), are currently undergoing clinical evaluation. Ziv-aflibercept forms monomeric complexes with VEGF-A, VEGF-B, and PlGF, which have a long half-life, allowing optimization of ziv-aflibercept doses and angiogenic blockage.
Conclusions:
Although antiangiogenic therapies have increased treatment options for cancer patients, their use is limited by a lack of established and standardized methodology to evaluate their efficacy in vivo. Circulating endothelial cells, hypertension, and several molecular and imaging-based markers have potential for use as biomarkers in these patients and may better define appropriate patient populations.
Insights
Assessing antiangiogenic therapies for cancer is crucial but challenging due to suboptimal efficacy and unknown patient responses. New biomarkers are needed to standardize evaluation and identify optimal patient populations for these treatments.
Area of Science:
- Oncology
- Molecular Biology
- Clinical Pharmacology
Background:
- Tumor growth and metastasis depend on angiogenesis, the formation of new blood vessels.
- Antiangiogenic therapies aim to inhibit tumor vascularization and are used in various cancer treatments.
- Despite advances, the optimal use of these therapies remains limited by challenges in efficacy assessment.
Purpose of the Study:
- To review key clinical issues in assessing the in vivo efficacy of antiangiogenic therapies for cancer.
- To highlight challenges in optimizing antiangiogenic treatment strategies.
- To explore potential biomarkers for patient selection and treatment monitoring.
Main Methods:
- Comprehensive literature review on antiangiogenic therapies in cancer.
- Emphasis on methods for assessing in vivo efficacy.
- Exploration of angiogenic escape mechanisms and alternative pathways.
Main Results:
- Antiangiogenic therapies, like bevacizumab targeting VEGF-A, show activity but have suboptimal use.
- Optimal dosing, duration, and combination strategies are not yet established.
- Alternative angiogenic pathways and multiligand-targeted agents like ziv-aflibercept are under investigation.
Conclusions:
- Standardized in vivo efficacy assessment methods for antiangiogenic therapies are lacking.
- Biomarkers such as circulating endothelial cells, hypertension, and molecular/imaging markers show promise.
- These biomarkers may help define appropriate patient populations for targeted antiangiogenic treatment.

