Antiangiogenic Drugs: Current Knowledge and New Approaches to Cancer Therapy

Mauriz, José L.; González‐Gallego, Javier

doi:10.1002/jps.21286

Cited by 26 publications

(17 citation statements)

References 190 publications

(189 reference statements)

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“…Several mechanism have been proposed, including inhibition of methionine aminopeptidase (MetAP-2)97 through covalent modification of a histidine98 and prevention of endothelial activation of Rac199. TNP-470 also affects cell cycle through activation of p53, leading to an increase in the G 1 cyclin-dependent kinase inhibitor p21 CIP/WAF and subsequent growth arrest100,101.…”

Section: Anti-angiogenesis Compoundsmentioning

confidence: 99%

See 1 more Smart Citation

Angiogenesis Inhibitors: Current Strategies and Future Prospects

Cook¹,

Figg²

2010

CA: A Cancer Journal for Clinicians

433

335

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Angiogenesis has become an attractive target for drug therapy because of its key role in tumor growth. An extensive array of compounds is currently in preclinical development, with many now entering the clinic and/or achieving approval from the US Food and Drug Administration. Several regulatory and signaling molecules governing angiogenesis are of interest, including growth factors (eg, vascular endothelial growth factor, platelet-derived growth factor, fibroblast growth factor, and epidermal growth factor), receptor tyrosine kinases, and transcription factors such as hypoxia inducible factor, as well as molecules involved in mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K) signaling. Pharmacologic agents have been identified that target these pathways, yet for some agents (notably thalidomide), an understanding of the specific mechanisms of antitumor action has proved elusive. The following review describes key molecular mechanisms and novel therapies that are on the horizon for antiangiogenic tumor therapy. CA Cancer J Clin 2010;60:222-243.

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Section: Anti-angiogenesis Compoundsmentioning

confidence: 99%

“…Cetuximab is a chimeric monoclonal antibody that binds to the inactive form of EGFR on the extracellular domain101. Cetuximab essentially prevents the ligand from being able to bind to the receptor and therefore any downstream signaling activation152.…”

Section: Anti-angiogenesis Compoundsmentioning

confidence: 99%

Angiogenesis Inhibitors: Current Strategies and Future Prospects

Cook¹,

Figg²

2010

CA: A Cancer Journal for Clinicians

433

335

View full text Add to dashboard Cite

show abstract

“…Hence, the inhibition of angiogenesis has been demonstrated to be one of the potentially more promising new approaches to anti-cancer therapy [Folkman, 2007;Harris, 1997]. Anti-angiogenic treatment strategies focus on the endothelial cell compartment rather than the tumor and offer several advantages over conventional chemotherapeutic agents, which have been extensively cited and reviewed elsewhere [Mauriz and Gonzalez-Gallego, 2008]. In previous reviews, agents with anti-angiogenic activity have been grouped into four different categories: (1) mechanism-based approaches; (2) endogenous inhibitors (of unknown mechanisms); (3) natural productbased approach; and (4) vascular targeting strategies [Carmeliet and Jain, 2000;Colman et al, 2000;Colman et al, 2001;Connell and Beebe, 2001;Dhanabal et al, 2005;Ferrara and Alitalo, 1999;Sund et al, 2005a,b].…”

Section: Angiogenesismentioning

confidence: 99%

Targeting tumor vascular endothelium: an emerging concept for cancer therapy

Mohanraj¹,

Karumanchi²,

Sukhatme³

2008

Drug Development Research

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Although traditional chemotherapeutic agents have saved thousands of lives over the years and delayed tumor progression, they have limited efficacy due to toxicity and lack of tumor cell selectivity. Recently some of the more promising anticancer therapy approaches tested and proven in clinical studies have used a combinatorial approach of using new molecularly targeted agents with standard therapies. In this regard, inhibition of angiogenesis represents a new approach to cancer therapy. To date, many antiangiogenic agents have been developed and are in different stages of clinical development. Targeting tumor cell-associated endothelial cells may represent a potential powerful adjunct to traditional cancer therapy. In this review, we provide an overview of different approaches involved in discovery and development of anti-angiogenic agents and discuss the clinical impact of these agents. Finally, we present and summarize some of the emerging concepts such as resistance to anti-angiogenic drugs, antiangiogenic therapy-related toxicity, and integrated treatment modalities. Drug Dev Res 69 : 340-351, 2008.

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“…This active targeting can result in an improvement in both the specificity of the drug for the tumor and its accumulation [14, 59-61]. However, the effectiveness of high affinity ligands is limited by their systemic toxicity, as their high affinity also promotes their interaction with the same receptor that is expressed in healthy tissues, albeit at lower levels [62, 63]. While multivalent ligand presentation can increase the avidity of receptor-ligand interactions, multivalent drug carriers experience the same problem of increased off-site targeting with increased affinity [59].…”

Section: Hyperthermia-triggered Multivalencymentioning

confidence: 99%

Drug delivery to solid tumors by elastin-like polypeptides

McDaniel¹,

Callahan²,

Chilkoti³

2010

Advanced Drug Delivery Reviews

190

150

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Thermally responsive elastin-like polypeptides (ELPs) are a promising class of recombinant biopolymers for the delivery of drugs and imaging agents to solid tumors via systemic or local administration. This article reviews four applications of ELPs to drug delivery, with each delivery mechanism designed to best exploit the relationship between the characteristic transition temperature (T t ) of the ELP and body temperature (T b ). First, when T t >> T b , small hydrophobic drugs can be conjugated to the C-terminus of the ELP to impart the amphiphilicity needed to mediate the self-assembly of nanoparticles. These systemically delivered ELP-drug nanoparticles preferentially localize to the tumor site via the EPR effect, resulting in reduced toxicity and enhanced treatment efficacy. The remaining three approaches take direct advantage of the thermal responsiveness of ELPs. In the second strategy, where T b < T t < 42 °C, an ELP-drug conjugate can be injected in conjunction with external application of mild hyperthermia to the tumor to induce ELP coacervation and an increase in concentration within the tumor vasculature. The third approach utilizes hydrophilic-hydrophobic ELP block copolymers that have been designed to assemble into nanoparticles in response to hyperthermai due to the independent thermal transition of the hydrophobic block, thus resulting in multivalent ligand display of a ligand for spatially enhanced vascular targeting. In the final strategy, ELPs with T t < T b are conjugated with radiotherapeutics, injtect intioa tumor where they undergo coacervation to form an injectable drug depot for intratumoral delivery. These injectable coacervate ELP-radionuclide depots display a long residence in the tumor and result in inhibition of tumor growth.

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Antiangiogenic Drugs: Current Knowledge and New Approaches to Cancer Therapy

Cited by 26 publications

References 190 publications

Angiogenesis Inhibitors: Current Strategies and Future Prospects

Angiogenesis Inhibitors: Current Strategies and Future Prospects

Targeting tumor vascular endothelium: an emerging concept for cancer therapy

Drug delivery to solid tumors by elastin-like polypeptides

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