Abstract：
UNLABELLED:Preclinical animal models are useful tools to better understand tumor initiation and progression and to predict the activity of an anticancer agent in the clinic. Ideally, these models should recapitulate the biological characteristics of the tumor and of the related tumor microenvironment (e.g. vasculature, immune cells) in patients. Even if several examples of translational success have been reported it is a matter of fact that clinical trials in oncology often fail to meet their primary endpoints despite encouraging preclinical data. For this reason, there is an increasing need of improved and more predictive models. This review aims to give an overview on existing mouse models for preclinical evaluation of cancer therapeutics and their applicability. Different types of mouse models commonly used for the evaluation of cancer therapeutics are described and considerations for a "fit-for purpose" application of these models for the evaluation of different cancer therapeutics dependent on their mode of action are outlined. Furthermore, considerations for study design and data interpretation to translatability of findings into the clinics are given. CONCLUSION:Detailed knowledge of the molecular/biological properties of the respective model, diligent experimental setup, and awareness of its limitations are indispensable prerequisites for the successful translational use of animal models.
journal_name
Pharmacol Therjournal_title
Pharmacology & therapeuticsauthors
Wartha K,Herting F,Hasmann Mdoi
10.1016/j.pharmthera.2014.01.001subject
Has Abstractpub_date
2014-06-01 00:00:00pages
351-61issue
3eissn
0163-7258issn
1879-016Xpii
S0163-7258(14)00011-4journal_volume
142pub_type
杂志文章,评审abstract：:While antibiotics revolutionized the treatment of infectious disease in the 20th century, bacterial resistance now threatens to render many of them ineffective. Aminoglycosides are a class of clinically important antibiotics used in the treatment of infections caused by Gram-positive and -negative organisms. They are ...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/s0163-7258(02)00197-3
更新日期：2002-02-01 00:00:00
abstract：:Brain-derived neurotrophic factor (BDNF) has emerged as a regulator of development, plasticity and, recently, addiction. Decreased neurotrophic activity may be involved in ethanol-induced neurodegeneration in the adult brain and in the etiology of alcohol-related neurodevelopmental disorders. This can occur through de...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2008.01.003
更新日期：2008-04-01 00:00:00
abstract：:Since the first description of their opioid properties three decades ago, dynorphins have increasingly been thought to play a regulatory role in numerous functional pathways of the brain. Dynorphins are members of the opioid peptide family and preferentially bind to kappa opioid receptors. In line with their localizat...
journal_title：Pharmacology & therapeutics
pub_type： 历史文章,杂志文章,评审
doi：10.1016/j.pharmthera.2009.05.006
更新日期：2009-09-01 00:00:00
abstract：:Minor groove binders are small molecules that form strong complexes with the minor groove of DNA. There are several structural types of which distamycin and netropsin analogues, oligoamides built from heterocyclic and aromatic amino acids, and bis-amidines separated by aromatic and heterocyclic rings are of particular...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2013.03.002
更新日期：2013-07-01 00:00:00
abstract：:Liver parenchyma shows a remarkable heterogeneity of the hepatocytes along the porto-central axis with respect to ultrastructure and enzyme activities resulting in different cellular functions within different zones of the liver lobuli. According to the concept of metabolic zonation, the spatial organization of the va...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/0163-7258(92)90055-5
更新日期：1992-01-01 00:00:00
abstract：:Evidence from experimental and clinical studies suggests the involvement of the endogenous opioid system in several neurologic and psychiatric disorders (Alzheimer's, Huntington's and Parkinson's diseases, drug-induced movement disorders, Gilles de la Tourette syndrome, stroke, ischemia, brain and spinal cord injury, ...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/0163-7258(90)90026-x
更新日期：1990-01-01 00:00:00
abstract：:The selective 5-HT2C receptor agonist lorcaserin, in conjunction with lifestyle modification, was approved by the FDA in 2012 for weight management. It has been marketed in the US as Belviq® since 2013. This article provides a review of the preclinical and clinical pharmacology of lorcaserin, including its pharmacokin...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2019.107417
更新日期：2020-01-01 00:00:00
abstract：:Evidence that the delta opioid receptor (DOR) is an attractive target for the treatment of brain disorders has strengthened in recent years. This receptor is broadly expressed in the brain, binds endogenous opioid peptides, and shows as functional profile highly distinct from those of mu and kappa opioid receptors. Ou...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2013.06.003
更新日期：2013-10-01 00:00:00
abstract：:Pancreatic ductal adenocarcinoma (PDAC) is a highly metastatic disease with a high mortality rate. Genetic and biochemical studies have shown that RAS signaling mediated by KRAS plays a pivotal role in disease initiation, progression and drug resistance. RAS signaling affects several cellular processes in PDAC, includ...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2016.09.003
更新日期：2016-12-01 00:00:00
abstract：:Apoptotic cell death mediated by the members of the tumor necrosis factor receptor family is an essential process involved in the regulation of cellular homeostasis during development, differentiation, and pathophysiological conditions. Among the cell death receptors comprising the tumor necrosis factor receptor super...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/s0163-7258(00)00096-6
更新日期：2000-12-01 00:00:00
abstract：:Fish oil supplementation has been reported to be generally beneficial in autoimmune, inflammatory and cardiovascular disorders. Most researchers have attributed these beneficial effects to the high content of omega-3 fatty acids in fish oil (FO). The effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2009.01.004
更新日期：2009-04-01 00:00:00
abstract：:The science of Tourette Syndrome (TS) is advancing at multiple levels of analysis and will be enhanced through the use of animal models. Particular challenges in the development of TS animal models reflect complex features of this disorder, including its waxing and waning course and its "invisible" sensory and psychic...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2005.05.003
更新日期：2005-12-01 00:00:00
abstract：:Poly (ADP-ribose) polymerase (PARP) inhibitors have transformed the therapeutic management of solid tumors, particularly ovarian cancer. Initially studied in BRCA deficient tumors, the Food and Drug Administration (FDA) indications have expanded to include other homologous recombination deficient tumors as well as bio...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2020.107588
更新日期：2020-09-01 00:00:00
abstract：:The past three decades have witnessed a welcome expansion of the therapeutic armamentarium for the management of pulmonary arterial hypertension (PAH). However, against this backdrop, there have been some notable disappointments in drug development. Here we use these as case studies to emphasize the importance of info...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2016.04.012
更新日期：2016-08-01 00:00:00
abstract：:Metabolic syndrome has been described as the association of insulin resistance, hypertension, hyperlipidemia and obesity. Its prevalence increased dramatically, mainly in developed countries. Animal models are essential to understand the pathophysiology of this syndrome. This review presents the murine models of metab...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2012.11.004
更新日期：2013-03-01 00:00:00
abstract：:Since the first reports on chemokine function, much information has been generated on the implications of these molecules in numerous physiological and pathological processes, as well as on the signaling events activated through their binding to receptors. Despite these extensive studies, no chemokine-related drugs ha...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2011.05.002
更新日期：2011-09-01 00:00:00
abstract：:Pharmacological agents, such as histamine H(2) receptor antagonists and acid pump inhibitors, are now the most frequently used treatment for such acid-related diseases as gastroduodenal ulcers and reflux esophagitis. Based on increased understanding of the precise mechanisms of gastric acid secretion at the level of r...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/s0163-7258(03)00015-9
更新日期：2003-04-01 00:00:00
abstract：:Several amphetamine analogs are potent psychostimulants and major drugs of abuse. In animal models, the psychomotor and reinforcing effects of amphetamine, methamphetamine (METH), 3,4-methylenedioxymethamphetamine (MDMA; Ecstasy), and methylphenidate (MPD; Ritalin) are thought to be dependent on increased extracellula...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2005.08.004
更新日期：2006-01-01 00:00:00
abstract：:Cardiovascular diseases cause more mortality and morbidity worldwide than any other diseases. Although many intracellular signaling pathways influence cardiac physiology and pathology, the mitogen-activated protein kinase (MAPK) family has garnered significant attention because of its vast implications in signaling an...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2014.05.013
更新日期：2014-11-01 00:00:00
abstract：:Ross River virus (RRV) is a mosquito-borne alphavirus indigenous to Australia and the Western Pacific region and is responsible for several thousand cases of human RRV disease (RRVD) per annum. The disease primarily involves polyarthritis/arthralgia, with many patients also presenting with rash, myalgia, fever, and/or...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2005.03.006
更新日期：2005-09-01 00:00:00
abstract：:Patients of congenital diseases such as Down syndrome (DS) and Duchenne muscular dystrophy (DMD) have abnormalities in their chromosomes and/or genes. Therefore, it has been considered that drug treatments can serve to do little for these patients more than to patch over each symptom temporarily when it arises. Althou...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2012.02.001
更新日期：2012-06-01 00:00:00
abstract：:The tumor microenvironment is increasingly recognized as a major factor influencing the success of therapeutic treatments and has become a key focus for cancer research. The progressive growth of a tumor results in an inability of normal tissue blood vessels to oxygenate and provide sufficient nutritional support to t...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2015.06.006
更新日期：2015-09-01 00:00:00
abstract：:The endothelins and sarafotoxins are two structurally related families of potent vasoactive peptides. Although the physiological functions of these peptides are not entirely clear, the endothelins are probably involved in pathophysiological conditions such as hypertension and heart failure. This review summarizes the ...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/0163-7258(92)90030-4
更新日期：1992-01-01 00:00:00
abstract：:A number of neuronal functions, including synaptic plasticity, depend on proper regulation of synaptic proteins, many of which can be rapidly regulated by phosphorylation. Neuronal activity controls the function of these synaptic proteins by exquisitely regulating the balance of various protein kinase and protein phos...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2006.06.003
更新日期：2006-12-01 00:00:00
abstract：:Polycyclic aromatic hydrocarbons (PAH) are carcinogens requiring metabolic activation to react with cellular macromolecules, the initial event in carcinogenesis. Cytochrome P450 mediates binding of PAH to DNA by two pathways of activation. One-electron oxidation to form radical cations is the major pathway of activati...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/0163-7258(92)90015-r
更新日期：1992-01-01 00:00:00
abstract：:It is surprising that only relatively recently has attention been directed to the characterization of the properties of acid ribonucleases (RNases), leading to some understanding of their biochemistry and their functional roles. The present review summarizes current progress in this field under the following general t...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/s0163-7258(98)00035-7
更新日期：1999-02-01 00:00:00
abstract：:The thyroid hormone (TH; 3,3',5,5'-tetra-iodothyronine and 3,3',5'-triiodothyronine) regulates growth, development, and critical metabolic functions. Thyroid diseases are among the most prevalent group of metabolic disorders in the Western world. TH exerts effects through complex biological pathways, which offer a wea...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/s0163-7258(02)00219-x
更新日期：2002-06-01 00:00:00
abstract：:The human epidermal growth factor receptor (HER) family members are targeted by a growing numbers of small molecules and monoclonal antibodies. Resistance against the epidermal growth factor receptor (EGFR) and HER2-targeting agents is a clinically relevant problem forcing research on optimizing targeting of the HER f...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2014.01.005
更新日期：2014-07-01 00:00:00
abstract：:Despite some recent declines, cardiovascular disease (CVD) remains the major cause of death in the United States and worldwide. Most recent advances in the treatment of CVD states have been produced by inhibition of mechanisms involved in disease progress. Many studies conducted in the last decade have illustrated inc...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/s0163-7258(00)00114-5
更新日期：2001-02-01 00:00:00
abstract：:Major depression is a debilitating and recurrent disorder with a substantial lifetime risk and a high social cost. Depressed patients generally display co-morbid symptoms, and depression frequently accompanies other serious disorders. Currently available drugs display limited efficacy and a pronounced delay to onset o...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2005.11.006
更新日期：2006-05-01 00:00:00
