Urokinase receptor antagonists: novel agents for the treatment of cancer.

Abstract:

:The interaction between the urokinase receptor (uPAR) and its ligand urokinase (uPA) mediates phenomena such as tissue remodelling, chemotaxis, tumour invasion, dissemination, proliferation, and angiogenesis. The broad-spectrum of biological processes that the uPA/uPAR interaction plays a role in has led researchers to speculate that this interaction may be a useful molecular target for therapeutic intervention in several pathological conditions, particularly in the prevention and inhibition of the dissemination of cancer cells. In syngeneic and xenograft murine tumour models, in which metastasis is driven by the uPA/uPAR interaction, inhibition of primary tumour growth, metastasis and angiogenesis has been shown with several proteins acting as uPAR antagonists. Immunohistochemistry, in conjunction with prognostic studies, has implicated the uPA/uPAR interaction in the dissemination of tumours, such as malignant melanoma, colon cancer, non-small cell lung cancer (NSCLC) and stomach cancer, as well as breast and ovarian carcinomas. A potential inhibitor of the uPA/uPAR interaction should result in a significant increase in the disease-free interval and survival time following resection of the primary tumour in a clinical Minimal Residual Disease (MRD) setting. Low molecular weight uPAR antagonists should be orally active, and have few side-effects, excellent bioavailability, favourable pharmacokinetic properties and a long half-life. Furthermore, these compounds should be able to inhibit the dissemination of cancer cells without the need for targeted drug and vector delivery.

authors

Weidle UH,König B

doi

10.1517/13543784.7.3.391

subject

Has Abstract

pub_date

1998-03-01 00:00:00

pages

391-403

issue

3

eissn

1354-3784

issn

1744-7658

journal_volume

7

pub_type

杂志文章
  • Novel agents for the treatment of polycythemia vera: an insight into preclinical research and early phase clinical trials.

    abstract:INTRODUCTION:Current treatment for polycythemia vera (PV) is limited and primarily targets thrombosis risk. Agents targeting distinct mechanisms of action within myeloproliferation are undergoing clinical evaluation to optimize efficacy, improve tolerance and augment long term disease complications. AREA COVERED:This ...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章

    doi:10.1080/13543784.2020.1782886

    authors: Padrnos L,Mesa R

    更新日期:2020-08-01 00:00:00

  • Insulin aspart: a novel rapid-acting human insulin analogue.

    abstract::In order to improve therapy and increase the quality of life for diabetic patients, it has been of significant interest to develop rapid-acting insulin preparations that mimic the physiological meal-time profile of insulin more closely than soluble human insulin. Insulin aspart (B28Asp human insulin) is a novel rapid-...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章

    doi:10.1517/13543784.8.9.1431

    authors: Gammeltoft S,Hansen BF,Dideriksen L,Lindholm A,Schäffer L,Trüb T,Dayan A,Kurtzhals P

    更新日期:1999-09-01 00:00:00

  • Trends in pioglitazone use among U.S. adults with type 2 diabetes and suspected nonalcoholic fatty liver disease.

    abstract::Background: We aimed to estimate population-based trends in the prevalence of coexisting type 2 diabetes (T2D) and suspected nonalcoholic fatty liver disease (NAFLD) and pioglitazone use among U.S. adults.Research design and methods: We conducted a cross-sectional analysis of the National Health and Nutrition Examinat...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章

    doi:10.1080/13543784.2020.1704731

    authors: Le P,Chaitoff A,Rothberg MB,McCullough A,Alkhouri N

    更新日期:2020-02-01 00:00:00

  • Neuroimmunophilin ligands: evaluation of their therapeutic potential for the treatment of neurological disorders.

    abstract::Neuroimmunophilin ligands are a class of compounds that hold great promise for the treatment of nerve injuries and neurological disease. In contrast to neurotrophins (e.g., nerve growth factor), these compounds readily cross the blood-brain barrier, being orally effective in a variety of animal models of ischaemia, tr...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章,评审

    doi:10.1517/13543784.9.10.2331

    authors: Gold BG

    更新日期:2000-10-01 00:00:00

  • VEGF Trap-Eye for the treatment of neovascular age-related macular degeneration.

    abstract:BACKGROUND:Age-related macular degeneration (AMD) affects > 14 million individuals worldwide. Although 90% of patients with AMD have the dry form, neovascular AMD accounts for the vast majority of patients who develop legal blindness. Until recently, few treatment options existed for treatment of neovascular AMD. The a...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章,评审

    doi:10.1517/13543780903201684

    authors: Dixon JA,Oliver SC,Olson JL,Mandava N

    更新日期:2009-10-01 00:00:00

  • Developments in the treatment of chronic hepatitis C.

    abstract::Hepatitis C virus is the most common chronic, blood-bourne infection, affecting 170 million people worldwide, approximately 3% of the global population. Of those infected with hepatitis C virus, 50 - 85% will develop chronic hepatitis C. Although hepatitis C is primarily a disease of the liver, a diagnosis is currentl...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章,评审

    doi:10.1517/13543784.11.4.515

    authors: Pockros PJ

    更新日期:2002-04-01 00:00:00

  • Recent advances in natriuretic peptides in congestive heart failure.

    abstract::Atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) are secreted by the heart and play important roles in the compensation of congestive heart failure with their vasodilating, natriuretic, antiproliferative, lusitropic and neurohumoral-modulating properties. Based on these beneficial properties, exog...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章,评审

    doi:10.1517/13543784.13.6.643

    authors: Boerrigter G,Burnett JC Jr

    更新日期:2004-06-01 00:00:00

  • Lenalidomide for the treatment of B-cell lymphoma.

    abstract:INTRODUCTION:Although the combination of an anti-CD20 monoclonal antibody and chemotherapy has widely improved survival of patients with B-cell lymphoma, the disease still relapses. A better understanding of the biology of lymphomas has highlighted the role of the cell of origin in response to treatment and outcome. Le...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章,评审

    doi:10.1080/13543784.2016.1208170

    authors: Garciaz S,Coso D,Schiano de Colella JM,Bouabdallah R

    更新日期:2016-09-01 00:00:00

  • Statins and neuroprotection.

    abstract::The beneficial effect of beta-hydroxy-beta-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) in primary prevention of coronary artery disease in those with hypercholesterolaemia and in secondary prevention in those with established coronary vascular disease are now well known. A growing body of eviden...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章,评审

    doi:10.1517/13543784.10.10.1847

    authors: Delanty N,Vaughan CJ,Sheehy N

    更新日期:2001-10-01 00:00:00

  • An overview of investigational toxin-directed therapies for the adjunctive management of Bacillus anthracis infection and sepsis.

    abstract:INTRODUCTION:Sepsis with Bacillus anthracis infection has a very high mortality rate despite appropriate antibiotic and supportive therapies. Over the past 15 years, recent outbreaks in the US and in Europe, coupled with anthrax's bioterrorism weapon potential, have stimulated efforts to develop adjunctive therapies to...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章,评审

    doi:10.1517/13543784.2015.1041587

    authors: Ohanjanian L,Remy KE,Li Y,Cui X,Eichacker PQ

    更新日期:2015-01-01 00:00:00

  • Fospropofol disodium, a water-soluble prodrug of the intravenous anesthetic propofol (2,6-diisopropylphenol).

    abstract:BACKGROUND:Today, propofol or 2,6-diisopropylphenol is the anesthetic mainly used for monitored anesthetic care sedation and during intravenous anesthesia. The formulation, a lipid macroemulsion, shows several disadvantages. Therefore, during the past years considerable scientific effort has been undertaken to find eit...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章,评审

    doi:10.1517/13543780903193063

    authors: Fechner J,Ihmsen H,Jeleazcov C,Schüttler J

    更新日期:2009-10-01 00:00:00

  • Investigational drugs for eating disorders.

    abstract::The eating disorders anorexia nervosa, bulimia nervosa and binge eating disorder are common, significant public health problems which are treated with nutritional, psychotherapeutic and pharmacological interventions. A number of drugs (mostly antidepressant drugs) are currently used in their treatment to some benefit,...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章,评审

    doi:10.1517/13543784.12.3.491

    authors: Crow S,Brown E

    更新日期:2003-03-01 00:00:00

  • Cardiac fibrosis: emerging agents in preclinical and clinical development.

    abstract:INTRODUCTION:Myocardial fibrosis is a remarkably dynamic process mediated by different molecular pathways that represent potential targets of novel therapeutic interventions. Transforming Growth Factor-beta (TGF-β), connective Tissue Growth Factor (cTGF) and Galectin-3 (Gal-3) represent the most promising targets on wh...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章

    doi:10.1080/13543784.2021.1868432

    authors: Spoladore R,Falasconi G,Fiore G,Di Maio S,Preda A,Slavich M,Margonato A,Fragasso G

    更新日期:2021-01-04 00:00:00

  • Pharmacological methods to overcome IFN-beta antibody formation in the treatment of multiple sclerosis.

    abstract::Diminished efficacy in terms of clinical relapses and lesion load on magnetic resonance images for patients developing neutralising antibodies (NAbs) to recombinant IFN-beta may be found in multiple sclerosis. NAbs become detectable over the first few years of therapy, disappearing during the treatment course in some ...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章,评审

    doi:10.1517/13543784.12.7.1153

    authors: Bagnato F,Pozzilli C

    更新日期:2003-07-01 00:00:00

  • Skin substitutes to enhance wound healing.

    abstract::Biologically-based skin substitutes have developed as commercial products over the last 5 years. The first generation includes the collagen-based synthetic device, Integra, and Alloderm, which is based on devitalised and cross-linked human dermis. These are used as dermal replacements for third degree burns. Within th...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章

    doi:10.1517/13543784.7.5.803

    authors: Mansbridge J

    更新日期:1998-05-01 00:00:00

  • Investigational therapies for celiac disease.

    abstract::Celiac disease is an autoimmune condition affecting genetically susceptible individuals. It is produced by the ingestion of gluten contained in wheat, rye, barley, and related products. The only treatment currently available is strict adherence to a gluten-free diet for life. This requirement for dietary compliance is...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章,评审

    doi:10.1517/13543780903369333

    authors: Rodrigo L

    更新日期:2009-12-01 00:00:00

  • Emerging therapeutic strategies for minimal change disease and focal and segmental glomerulosclerosis.

    abstract:INTRODUCTION:Minimal change disease (MCD) and Focal and segmental glomerulosclerosis (FSGS) are two of the major causes of nephrotic syndrome (NS) in children and adults. According to KDIGO (Kidney Disease: Improving Global Outcomes) guidelines, the treatment of adult primary MCD and FSGS should be based on immunosuppr...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章,评审

    doi:10.1080/13543784.2018.1540587

    authors: Siligato R,Cernaro V,Nardi C,De Gregorio F,Gembillo G,Costantino G,Conti G,Buemi M,Santoro D

    更新日期:2018-11-01 00:00:00

  • TNP-470: an angiogenesis inhibitor in clinical development for cancer.

    abstract::TNP-470, an analogue of fumagillin, has been shown to inhibit angiogenesis in vitro and in vivo. In 1992, TNP-470 entered clinical development for cancer as an anti-angiogenic agent. It is currently in Phase I/II trials in Kaposi's sarcoma, renal cell carcinoma, brain cancer, breast cancer, cervical cancer and prostat...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章,评审

    doi:10.1517/13543784.9.6.1383

    authors: Kruger EA,Figg WD

    更新日期:2000-06-01 00:00:00

  • Therapeutic targeting of EGFR-activated metabolic pathways in glioblastoma.

    abstract:INTRODUCTION:The highly divergent histological heterogeneities, aggressive invasion and extremely poor response to treatment make glioblastoma (GBM) one of the most lethal and difficult cancers in humans. Among key elements driving its behavior is epidermal growth factor receptor (EGFR), however, neither traditional th...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章,评审

    doi:10.1517/13543784.2013.806484

    authors: Gao Q,Lei T,Ye F

    更新日期:2013-08-01 00:00:00

  • Doripenem: an expected arrival in the treatment of infections caused by multidrug-resistant Gram-negative pathogens.

    abstract:BACKGROUND:Potent new drugs against multidrug-resistant Gram-negative bacteria, namely Pseudomonas aeruginosa and Acinetobacter spp. and pan-drug-resistant Klebsiella pneumoniae, which constitute an increasing medical threat, are almost absent from the future pharmaceutical pipeline. OBJECTIVE:This drug evaluation foc...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章,评审

    doi:10.1517/13543784.17.5.749

    authors: Poulakou G,Giamarellou H

    更新日期:2008-05-01 00:00:00

  • Inhibitors of cyclic nucleotide phosphodiesterase PDE3 as adjunct therapy for dilated cardiomyopathy.

    abstract::PDE3 cyclic nucleotide phosphodiesterases are important in cyclic AMP (cAMP) and possibly cyclic GMP-mediated signalling in cardiac and vascular smooth muscle myocytes. Drugs that inhibit these enzymes have inotropic and vasodilatory actions that have proven useful in the short-term treatment of contractile failure an...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章,评审

    doi:10.1517/13543784.11.11.1529

    authors: Movsesian MA,Alharethi R

    更新日期:2002-11-01 00:00:00

  • The Annual European Congress of Rheumatology: recent advances in the treatment of rheumatic diseases. Lisbon, Portugal, June 18-21, 2003.

    abstract::The topics discussed at this conference covered many aspects of the pathogenesis, epidemiology, diagnosis and treatment of rheumatic diseases, from the search of new therapeutic targets and evaluation of new diagnostic techniques to preclinical and clinical development of novel therapies. This contribution focuses pri...

    journal_title:Expert opinion on investigational drugs

    pub_type:

    doi:10.1517/13543784.12.10.1713

    authors: Hellmich B,Gross WL

    更新日期:2003-10-01 00:00:00

  • Development of new cancer therapeutic agents targeting mitosis.

    abstract::Targeting cellular proliferation persists as a mainstay of cancer therapeutic strategy. Although microtubule-targeting drugs (such as taxanes and vinca alkaloids) have been used successfully in the clinic to treat a variety of cancers, they carry substantial liabilities that have spurred drug companies to aggressively...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章,评审

    doi:10.1517/13543784.15.11.1411

    authors: Miglarese MR,Carlson RO

    更新日期:2006-11-01 00:00:00

  • Histone deacetylase inhibitors in clinical development.

    abstract::In addition to a variety of other novel agents, interest in histone deacetylase inhibitors (HDACIs) as antineoplastic drugs has recently accelerated and increasing numbers of these compounds have entered clinical trials in humans. HDACIs represent a prototype of molecularly targeted agents that perturb signal transduc...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章,评审

    doi:10.1517/13543784.13.1.21

    authors: Rosato RR,Grant S

    更新日期:2004-01-01 00:00:00

  • Armodafinil: a new treatment for excessive sleepiness.

    abstract:BACKGROUND:Armodafinil is a wake-promoting agent developed by Cephalon that was approved in mid-2007 for the treatment of excessive sleepiness associated with narcolepsy, obstructive sleep apnea and shift work disorder. It is the R-enantiomer of the compound modafinil. Like modafinil, the mechanism of action for armoda...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章,评审

    doi:10.1517/13543784.17.4.565

    authors: Lankford DA

    更新日期:2008-04-01 00:00:00

  • Targeting enzymes to cancers--new developments.

    abstract::Two methods of using tumour located enzymes have been described. These are antibody directed enzyme prodrug therapy (ADEPT) and macromolecule directed enzyme prodrug therapy (MDEPT), where the tumour located enzyme converts a non-toxic prodrug into a cytotoxic drug at tumour sites. The alternative use of tumour locate...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章

    doi:10.1517/13543784.8.2.161

    authors: Bagshawe KD,Burke PJ,Knox RJ,Melton RG,Sharma SK

    更新日期:1999-02-01 00:00:00

  • The prospects for combination therapy with capecitabine in the rapidly evolving treatment landscape of renal cell carcinoma.

    abstract:INTRODUCTION:Although significant advances have been made in the treatment of advanced renal cell carcinoma (RCC), patients still develop resistance to standard therapies and require the administration of subsequent lines of treatment. New therapeutic approaches are thus imperative to improve the prognosis for patients...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章,评审

    doi:10.1080/13543784.2018.1427731

    authors: Bilen MA,Carlisle JW,Sonpavde G

    更新日期:2018-02-01 00:00:00

  • Immunotherapy in atopic dermatitis.

    abstract::Atopic dermatitis (AD) is a common inflammatory disease involving the skin and often other organs and systems, mainly respiratory. A definitive general consensus on the AD pathogenesis has not yet been established, however several lines of evidence suggest that T-cells play a crucial role in priming AD early-stage les...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章,评审

    doi:10.1517/13543784.10.1.49

    authors: Mastrandrea F

    更新日期:2001-01-01 00:00:00

  • Therapeutic potential of cyclic nucleotide phosphodiesterase inhibitors in heart failure.

    abstract::There are several reasons to believe that agents that augment cAMP-mediated signalling in cardiac myocytes should have beneficial effects in patients with heart failure. However, clinical trials of first-generation cyclic nucleotide phosphodiesterase (PDE3) inhibitors, which raise cAMP content by blocking its hydrolys...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章,评审

    doi:10.1517/13543784.9.5.963

    authors: Movsesian MA

    更新日期:2000-05-01 00:00:00

  • The development of antibody delivery systems to target cancer with highly potent maytansinoids.

    abstract::Improving the tumour selectivity of cytotoxic drugs through conjugation to tumour-reactive monoclonal antibodies may lead to novel, more potent agents for cancer therapy. The maytansinoid drugs are 100- to 1000-fold more cytotoxic in vitro than current clinical anticancer drugs. We recently demonstrated that conjugati...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章

    doi:10.1517/13543784.6.2.169

    authors: Liu C,Chari RV

    更新日期:1997-02-01 00:00:00