Abstract：
:As our ability to provide in-depth, patient-specific characterisation of the molecular alterations within tumours rapidly improves, it is becoming apparent that new approaches will be required to leverage the power of this data and derive the full benefit for each individual patient. Systems biology approaches are beginning to emerge within this field as a potential method of incorporating large volumes of network level data and distilling a coherent, clinically-relevant prediction of drug response. However, the initial promise of this developing field is yet to be realised. Here we argue that in order to develop these precise models of individual drug response and tailor treatment accordingly, we will need to develop mathematical models capable of capturing both the dynamic nature of drug-response signalling networks and key patient-specific information such as mutation status or expression profiles. We also review the modelling approaches commonly utilised within this field, and outline recent examples of their use in furthering the application of systems biology for a precision medicine approach to cancer treatment.
journal_name
Pharmacol Therjournal_title
Pharmacology & therapeuticsauthors
Hastings JF,O'Donnell YEI,Fey D,Croucher DRdoi
10.1016/j.pharmthera.2020.107555subject
Has Abstractpub_date
2020-08-01 00:00:00pages
107555eissn
0163-7258issn
1879-016Xpii
S0163-7258(20)30083-8journal_volume
212pub_type
杂志文章,评审abstract：:Although potent effects of psychoactive drugs on circadian rhythms were first described over 30 years ago, research into the reciprocal relationship between the reward system and the circadian system - and the impact of this relationship on addiction - has only become a focus in the last decade. Nonetheless, great pro...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2018.03.003
更新日期：2018-08-01 00:00:00
abstract：:Hyperkinetic movement disorders comprise a variety of conditions characterized by involuntary movements, which include but are not limited to tardive dyskinesia, chorea associated with Huntington's Disease, and tic disorders. The class of medications that have been used to treat these conditions includes Vesicular Mon...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2020.107580
更新日期：2020-08-01 00:00:00
abstract：:Mechanistic insights of cancer immunology have led to the development of immune checkpoint blockade therapy (ICBT), which has elicited a remarkable clinical response in some cancer patients. Increasing evidence suggests that activation of oncogenic pathways, such as RAS/RAF/MAPK and PI3K signaling, impairs the antitum...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2017.07.004
更新日期：2018-01-01 00:00:00
abstract：:Protein phosphorylation is the major post-translational modification used by eukaryotic cells to control cellular signaling. Protein kinases have emerged as attractive drug targets because heightened protein kinase activity has been associated with several proliferative diseases, most notably cancer and restenosis. Un...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/s0163-7258(98)00060-6
更新日期：1999-05-01 00:00:00
abstract：:The cardiovascular system is capable of robust changes in response to physiologic and pathologic stimuli through intricate signaling mechanisms. The area of metabolism has witnessed a veritable renaissance in the cardiovascular system. In particular, the post-translational β-O-linkage of N-acetylglucosamine (O-GlcNAc)...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2013.11.005
更新日期：2014-04-01 00:00:00
abstract：:In recent years there has been an explosion of interest in how genes regulate alcohol drinking and contribute to alcoholism. This work has been stimulated by the completion of the human and mouse genome projects and the resulting availability of gene microarrays. Most of this work has been performed in drinking animal...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2009.09.002
更新日期：2009-12-01 00:00:00
abstract：:The small heat shock proteins (HSPs) HSP20, HSP27 and alphaB-crystallin are chaperone proteins that are abundantly expressed in smooth muscles are important modulators of muscle contraction, cell migration and cell survival. This review focuses on factors regulating expression of small HSPs in smooth muscle, signaling...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2008.04.005
更新日期：2008-07-01 00:00:00
abstract：:Increasing evidence of a critical role played by the bronchial epithelium in airway homeostasis is opening new therapeutic avenues. Its unique situation at the interface with the environment suggests that the subtle regulation orchestrated by the epithelium between tolerance and specific immune response might be impai...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2013.07.008
更新日期：2013-12-01 00:00:00
abstract：:This review focuses on the chemical and enzymatic aspects of the reductive activation of mitomycin C, its disulfide analogs KW-2149 and BMS-181174, and, in less detail, FR66979 and FR900482, newly discovered antitumor antibiotics related to mitomycins. Furthermore, structural aspects of DNA damage induced by these dru...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/s0163-7258(97)00088-0
更新日期：1997-10-01 00:00:00
abstract：:The "late sodium current" (I(NaL)) is a sustained component of the fast Na+ current of cardiac myocytes and neurons. As recently appreciated, common neurological and cardiac conditions are associated with abnormal I(NaL) enhancement, which may contribute to the pathogenesis of both electrical and contractile dysfuncti...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2008.06.001
更新日期：2008-09-01 00:00:00
abstract：:Natriuretic peptides play a critical role in coordination of fluid/electrolyte balance and vascular tone. The renal effects of circulating atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are distinct from the paracrine effects of vascular C-type natriuretic peptide (CNP). CNP is widely expressed t...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2004.08.011
更新日期：2005-02-01 00:00:00
abstract：:Thioredoxin 1 (Trx 1) is a 12-kDa protein with redox-active dithiol in the active site -Cys-Gly-Pro-Cys- that is ubiquitously present in the human body. Trx 1 is a defensive protein induced by various stresses and has anti-oxidative, anti-apoptotic and anti-inflammatory effects. The anti-oxidative effect of Trx 1 is m...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2010.04.004
更新日期：2010-09-01 00:00:00
abstract：:Glucose-6-phospate dehydrogenase (G6PD) deficiency is estimated to affect more than 400 million people world-wide. This X-linked genetic deficiency puts stress on red blood cells (RBC), which may be further augmented under certain pathophysiological conditions and drug treatments. These conditions can cause hemolytic ...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2020.107788
更新日期：2020-12-14 00:00:00
abstract：:Protein tyrosine kinases (PTKs) play a key role in normal cell and tissue development. Enhanced PTK activity is intimately correlated with proliferative diseases, such as cancers, leukemias, psoriasis, and restenosis. This realization prompted us to systematically synthesize tyrosine phosphorylation inhibitors (tyrpho...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/s0163-7258(98)00066-7
更新日期：1999-05-01 00:00:00
abstract：:Cytotoxic drug-induced nausea and vomiting are the side effects most feared by cancer patients. Emesis is an instinctive defense reaction caused by the somatoautonomic nerve reflex, which is integrated in the medulla oblongata. Emesis caused by cytotoxic drugs such as cisplatin is associated with an increase in the co...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/s0163-7258(03)00057-3
更新日期：2003-08-01 00:00:00
abstract：:In the past 4 years, RNA interference (RNAi) has become widely used as an experimental tool to analyse the function of mammalian genes, both in vitro and in vivo. By harnessing an evolutionary conserved endogenous biological pathway, first identified in plants and lower organisms, double-stranded RNA (dsRNA) reagents ...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2005.03.004
更新日期：2005-08-01 00:00:00
abstract：:The tropomyosin receptor kinase (TRK) family includes TRKA, TRKB, and TRKC proteins, which are encoded by NTRK1, NTRK2 and NTRK3 genes, respectively. Binding of neurotrophins to TRK proteins induces receptor dimerization, phosphorylation, and activation of the downstream signaling cascades via PI3K, RAS/MAPK/ERK, and ...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2017.02.006
更新日期：2017-05-01 00:00:00
abstract：:Common arrhythmias, particularly atrial fibrillation (AF) and ventricular tachycardia/fibrillation (VT/VF) are a major public health concern. Classic antiarrhythmic (AA) drugs for AF are of limited effectiveness, and pose the risk of life-threatening VT/VF. For VT/VF, implantable cardiac defibrillators appear to be th...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2011.03.003
更新日期：2011-11-01 00:00:00
abstract：:The pharmaceutical industry offers the world's population alleviation and cure from a variety of medical conditions, while also contributing to the economic performance of many countries. The potential importance of these characteristics have made the industry an area of intense debate, criticism and praise. This revi...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/0163-7258(95)00002-x
更新日期：1995-05-01 00:00:00
abstract：:The aim of the present paper was to present an overview of the current status of the methods used to predict the magnitude of pharmacokinetic drug-drug interactions (DDIs) which are caused by apparent changes in cytochrome P450 (CYP) activity with an emphasis on a method using in vivo information. In addition, more th...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2009.10.011
更新日期：2010-02-01 00:00:00
abstract：:The nuclear transport proteins, importins and exportins (karyopherin-β proteins), may play an important role in cancer by transporting key mediators of oncogenesis across the nuclear membrane in cancer cells. During nucleocytoplasmic transport of tumor suppressor proteins and cell cycle regulators during the processin...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2016.03.020
更新日期：2016-08-01 00:00:00
abstract：:Neurodegenerative diseases represent some of the most devastating neurological disorders, characterized by progressive loss of the structure and function of neurons. Current therapy for neurodegenerative disorders is limited to symptomatic treatment rather than disease modifying interventions, emphasizing the desperat...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2020.107705
更新日期：2020-10-09 00:00:00
abstract：:RSV infection of the lower respiratory tract in infants is the leading cause of pediatric hospitalizations and second to malaria in causing infant deaths worldwide. RSV also causes substantial morbidity in immunocompromised and elderly populations. The only available therapeutic is a prophylactic drug called Palivizum...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2020.107712
更新日期：2020-10-27 00:00:00
abstract：:During the last decade, rigorous scientific methods have been applied to determine the effects of cannabinoids on nociceptive neurotransmission. Cannabinoids have been observed to markedly decrease signalling in specific neural pathways that transmit messages about pain. These effects were found to be due to the suppr...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/s0163-7258(02)00252-8
更新日期：2002-08-01 00:00:00
abstract：:Three separate experimental approaches, using site-selective cAMP analogs, antisense strategy and retroviral vector-mediated gene transfer, have provided evidence that two isoforms, the RI- and RII-regulatory subunits of cAMP-dependent protein kinase, have opposite roles in cell growth and differentiation; RI being gr...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/0163-7258(93)90010-b
更新日期：1993-11-01 00:00:00
abstract：:Pokeweed antiviral protein (PAP) is a ribosome-inactivating protein (RIP) that inactivates ribosomes by the removal of a single adenine from ribosomal RNA. The studies summarized in our review concern the nature and application of this novel therapeutic agent. We describe how researchers continue to elucidate the stru...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/0163-7258(92)90053-3
更新日期：1992-01-01 00:00:00
abstract：:There is clear evidence that CB(2), historically referred to as the peripheral cannabinoid receptor, mediates many of the immune modulatory effects of cannabinoids. However, cannabinoid receptors cannot be classified simply as central or peripheral since CB(2) has been shown to play a role in the central nervous syste...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2012.12.004
更新日期：2013-03-01 00:00:00
abstract：:Diabetes is a debilitating disease characterized by chronic hyperglycemia and is often associated with obesity. With diabetes and obesity incidence on the rise, it is imperative to develop novel therapeutics that will not only lower blood glucose levels, but also combat the associated obesity. The G protein-coupled re...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2012.05.009
更新日期：2012-09-01 00:00:00
abstract：:Neutrophils form an essential part of innate immunity against infection. Cancer chemotherapy-induced neutropenia (CCIN) is a condition in which the number of neutrophils in a patient's bloodstream is decreased, leading to increased susceptibility to infection. Granulocyte colony-stimulating factor (GCSF) has been the ...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2019.107403
更新日期：2019-12-01 00:00:00
abstract：:The RNA-dependent P1/eIF-2 alpha protein kinase is a highly specific protein-serine/threonine kinase that catalyzes the phosphorylation of the alpha subunit of protein synthesis initiation factor eIF-2. The kinase plays a central role in translational control. The activity of the kinase is regulated by a variety of na...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/0163-7258(92)90005-k
更新日期：1992-01-01 00:00:00
