Abstract：
:Rational approaches to targeted cancer therapy have begun to predominate the pipelines of oncology drug development. Our rapidly increasing understanding of the "wiring" of tumor cells and the vulnerabilities of such cells that can potentially be exploited through targeted treatments has opened up enormous opportunities for improved therapies. Accumulating evidence suggests that many of these vulnerabilities reflect states of dependency or "addiction" that are unique to cancer cells (versus normal cells). Such addiction can arise due to a strict dependency on a single activated oncogene, a cell lineage-specific factor, or even to a non-oncogene, and identifying these "Achilles' heels" within individual tumors remains an important challenge to the development of targeted therapies. Recent technology advances that facilitate high-throughput genomic analysis of tumor specimens and genome-wide RNA interference screening in cancer cell lines are key among the newly developed tools that are beginning to reveal novel context-dependent therapeutic targets, and the rapidly increasing application of these technologies by a large number of laboratories will undoubtedly lead to more effective cancer therapies in the near future. Here, we review the various forms of cancer cell addiction and their relevance to the discovery of novel therapeutic targets.
journal_name
Biochem Pharmacoljournal_title
Biochemical pharmacologyauthors
Sharma SV,Settleman Jdoi
10.1016/j.bcp.2010.03.001subject
Has Abstractpub_date
2010-09-01 00:00:00pages
666-73issue
5eissn
0006-2952issn
1873-2968pii
S0006-2952(10)00165-6journal_volume
80pub_type
杂志文章,评审abstract：:In this study we investigated whether NADH fluorescence levels changed in response to low or high rates of electrical stimulation in single ventricular myocytes isolated from rat and guinea-pig hearts, either during a single contraction or upon sustained electrical stimulation of cells. NADH levels were determined fro...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(98)00016-1
更新日期：1998-07-15 00:00:00
abstract：:Oxysterols possess anti-proliferative properties that may be used with much effect in the treatment of cancer. We have demonstrated previously that 7 beta-hydroxycholesterol (7b-HC) provokes both metabolic stress, as witnessed by AMPK activation, and changes in lipid raft composition in C6 glioblastoma cells. These ob...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2013.03.012
更新日期：2013-07-01 00:00:00
abstract：:The effects of the basic polypeptide melittin on islet phospholipid degradation and insulin release were studied in static incubations of intact rat islets as a possible model of endogenous phospholipase A2 (PLA2) activation. Melittin (2 micrograms/ml) increased [3H]-arachidonic acid [( 3H]-AA) release from prelabeled...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(86)90438-7
更新日期：1986-10-01 00:00:00
abstract：:Metformin, a commonly used agent in the treatment of type 2 diabetes, is also associated with reduced risk of cancer development and improvement in cancer survival. Although much is known about metformin, the mechanisms behind its anti-cancer properties are not fully understood. In this study we addressed the role of ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2018.09.015
更新日期：2018-10-01 00:00:00
abstract：:Clinical use of fibrate hypolipidaemic agents has been associated with an increased incidence of hepatobiliary dysfunction including increased bile lithogenicity, gallstone formation, and cholestasis. The hepatic transport of bile acids plays an important role in bile formation and flow, and interference with the hepa...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(97)00146-9
更新日期：1997-07-01 00:00:00
abstract：:A series of protein modifying reagents were tested for their effects on the specific binding of [3H]MK801 to adult rat brain membranes. N-Bromosuccinimide, acetyl imidazole, 2,3-butanedione, 5,5'-dithiobis-(2-nitrobenzoic acid) and dithiothreitol all had no significant effect on binding. The carboxylic acid residue mo...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(93)90133-h
更新日期：1993-02-09 00:00:00
abstract：:Endothelins exert their physiological effects through interaction with cell surface receptors that are members of the G-protein-coupled receptor family. The endothelin receptor subtype B (ET(B) receptor) is abundantly expressed in rat cerebellum. Since agonist binding to G-protein-coupled receptors may be modulated by...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(01)00706-7
更新日期：2001-09-01 00:00:00
abstract：:Since ginsenoside-Rg(3), one of the panaxadiol saponins isolated from the ginseng root, significantly inhibited the secretion of catecholamines from bovine adrenal chromaffin cells stimulated by acetylcholine (ACh), the properties of ginsenoside-Rg(3) inhibition were investigated. Although ginsenoside-Rg(3) inhibited ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(01)00743-2
更新日期：2001-10-01 00:00:00
abstract：:Increasing evidence supports NLRP3 inflammasome as a new target to control inflammation. Dysregulation of NLRP3 inflammasome has been reported to be involved in the pathogenesis of several human inflammatory diseases. However, no NLRP3 inflammasome inhibitors are available in clinic. Terpenoids are natural products wi...
journal_title：Biochemical pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.bcp.2019.113739
更新日期：2020-02-01 00:00:00
abstract：:The purpose of this study was to investigate in rats the effects of three anthracyclines, pirarubicin, doxorubicin and epirubicin on gastric prostaglandin E2 (PGE2) metabolism and phospholipase A2 (PLA2, EC 3.1.1.4) activity. The level of the membrane precursor, arachidonic acid, and the stability of the membrane were...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(93)90509-u
更新日期：1993-08-03 00:00:00
abstract：:The effects of physiological and pathological concentrations of glucocorticoids were investigated using the glucocorticoid antagonist RU486 and the synthetic glucocorticoid dexamethasone, respectively. The effects of these treatments on the concentrations of glutamine and other amino acids in skeletal muscle and plasm...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(90)90505-f
更新日期：1990-09-01 00:00:00
abstract：:This study investigated the role of endothelium- and smooth muscle-dependent mechanisms in the interaction of cyclosporine (CyA), an immunosuppressant drug, with beta-adrenoceptor (isoprenaline)-mediated relaxations in isolated rat aortas precontracted with phenylephrine. CyA effects were assessed in the absence and p...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2006.10.015
更新日期：2007-02-01 00:00:00
abstract：:The protein tyrosine kinase (PTK) inhibitor genistein has been demonstrated to inhibit platelet-activating factor-stimulated prostaglandin E2 (PGE2) production in lipopolysaccharide (LPS)-primed P388D1 macrophage-like cells (Glaser et al., J Biol Chem 265: 8658-8664, 1990). Therefore, the role of PTK in eicosanoid bio...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(93)90147-o
更新日期：1993-02-09 00:00:00
abstract：:The influence of anionic groups on interaction of nucleophilic sulfur compounds with the purified hog liver flavin-containing monooxygenase was evaluated from kinetic constants obtained with various dithiobenzoates, thiolbenzoates, and thiolalkylcarboxylic acids. All compounds tested bearing a single negative charge l...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(87)90391-1
更新日期：1987-01-01 00:00:00
abstract：:Multiple sclerosis (MS) is a severe chronic T cell-mediated autoimmune inflammatory disease of the central nervous system (CNS), the existing therapy of which is only partially effective and is associated with undesirable side effects. Euphol, an alcohol tetracyclic triterpene, has a wide range of pharmacological prop...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2011.11.026
更新日期：2012-02-15 00:00:00
abstract：:The inhibition of rat liver monoamine oxidase by a number of N-propargyl and alpha-methyl amine derivatives has been examined. The results indicate that alpha-methyl-substituted primary and secondary amine derivatives tend to show selectivity as reversible inhibitors towards the A-form of the enzyme. The structural fe...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(82)90012-0
更新日期：1982-04-01 00:00:00
abstract：:Enhanced aggregation of platelets was observed in platelet-rich plasma, but not in washed platelet suspension (WPS), during acute inflammation in rats. Incubation of WPS with inflammatory plasma increased the aggregatory response to ADP, but the plasma itself did not cause aggregation of platelets. It potentiated the ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(90)90699-l
更新日期：1990-07-15 00:00:00
abstract：:Most studies have reported an up-regulation of retinoic acid receptor (RAR) mRNA expression by all-trans retinoic acid (RA). We aimed to study the effect of RA on RAR protein levels in MCF-7 human breast cancer cells. Incubation of these cells with 10(-6) M RA induced a rapid breakdown of both RARalpha and RARgamma in...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(01)00600-1
更新日期：2001-06-01 00:00:00
abstract：:The non-sedating anti-histamine, loratadine [ethyl 4-(8-chloro-5,6-dihydro-11H-benzo[5,6]-cyclohepta[1,2-b]pyridin- 11-ylidene-1-piperidinecarboxylate], was administered orally in the diet to mature male rats at dosages of 4, 10 and 25 mg/kg/day for 2 weeks. The effects of these treatments on liver microsomal cytochro...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(92)90176-j
更新日期：1992-05-28 00:00:00
abstract：:The kinetics of methotrexate inhibition of dihydrofolate reductase from Neisseria gonorrhoeae have been investigated. Methotrexate was shown to be a tight-binding inhibitor (Kt = 13 pM) competitive with dihydrofolate. However, "stoichiometric" or "pseudoirreversible" inhibition could not be demonstrated. Progress curv...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(84)90579-3
更新日期：1984-07-01 00:00:00
abstract：:The crystal structure of the anthraquinone derivative 1,8-bis-(2-diethylaminoethylamino)-anthracene-9,10-dione has been established. This compound was prepared as a potential DNA-intercalating agent based on the proven intercalators doxorubicin and mitoxantrone. Its DNA-binding properties have been examined experiment...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(83)90095-3
更新日期：1983-09-15 00:00:00
abstract：:Epidermal growth factor (EGF) rapidly stimulates the release of arachidonic acid in A549 cells by a mechanism that is sensitive to pertussis toxin [1]. We show that EGF treatment of A549 cells stimulates phosphorylation of cytosolic phospholipase A2 (cPLA2) through a mechanism that is similarly inhibited by pertussis ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(95)02442-5
更新日期：1996-07-26 00:00:00
abstract：:(1) As a first step in studying the kinetics of the lipolytic system of rat adipocytes, the day-to-day variation between dose-response curves has been analysed. (2) Methods are described for the evaluation of large quantities of data relating noradrenaline to lipolysis. (3) A 'clustering' technique is presented which ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(82)90455-5
更新日期：1982-03-01 00:00:00
abstract：:It has been hypothesized that oxidative modification of low density lipoprotein plays a key role in the pathogenesis of atherosclerosis. In order to elucidate the role of lipid oxidation and its inhibition in vivo, apolipoprotein E and alpha-tocopherol (alphaT) transfer protein double knockout (ApoE(-/-)alpha-TTP(-/-)...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2007.07.020
更新日期：2007-10-01 00:00:00
abstract：:Regional adrenergic function is difficult to assess in humans. Tyramine given through a microdialysis probe may be a useful tool in this regard. However, tyramine data is hard to interpret given the drug's complex mode of action. We characterized the response to tyramine, isoproterenol, and dopamine in adipose tissue ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2006.09.004
更新日期：2006-12-15 00:00:00
abstract：:The aim of this study was to find the peptide ligands to inhibit Candida albicans secreted aspartyl proteinase 2 (Sap2). First, a ligand library, containing 300 different peptides, was constructed, and their interaction with Sap2 was separately calculated by molecular dynamic software. Second, 10 peptide ligands with ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2014.05.020
更新日期：2014-08-15 00:00:00
abstract：:Taxol-based chemotherapy is widely used as the first-line treatment for non-small cell lung cancer (NSCLC), however, the subsequent development of taxol-resistance is a major concern and challenge, resulting in tumor relapse and poor prognosis. Given the complex nature of taxol-resistance, we further delved into its m...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2019.113733
更新日期：2020-01-01 00:00:00
abstract：:Previous studies of platinum(II) compounds with bidentate leaving ligands have emphasized the contrast between the stability of the bidentate leaving ligand in vitro (T1/2 greater than 11 days in water) and the apparent reactivity of these bidentate platinum compounds in vivo. However, none of these studies actually m...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(88)90646-6
更新日期：1988-09-01 00:00:00
abstract：:Novel hydroxynaphthoquinones have been shown to be potent and selective inhibitors of mitochondrial electron transport in the protozoan Eimeria tenella, inhibiting at concentrations of 10(-10) to 10(-11)M. The primary site of electron transport inhibition has been localized to the ubiquinol-cytochrome c reductase span...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(84)90581-1
更新日期：1984-07-01 00:00:00
abstract：:A novel enzyme that converts dihydroxyphenylacetic acid (DOPAC) to dihydroxyphenylethanol (DOPET) was found to be present in the microdialysate of the rat brain. The enzyme, named DOPAC reductase, was inhibited by EDTA and stimulated by divalent cations like Zn2+, Mn2+, Co2+ and Cu2+. Its Km, pH optimum and temperatur...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(95)02092-6
更新日期：1995-10-26 00:00:00
