Abstract:
:The advent of drugs targeting tumor-associated prosurvival alterations of cancer cells has changed the interest of antitumor drug development from cytotoxic drugs to target-specific agents. Although single-agent therapy with molecularly targeted agents has shown limited success in tumor growth control, a promising strategy is represented by the development of rational combinations of target-specific agents and conventional antitumor drugs. Activation of survival/antiapoptotic pathways is a common feature of cancer cells that converge in the development of cellular resistance to cytotoxic agents. The survival pathways implicated in cellular response to drug treatment are primarily PI3K/Akt and Ras/MAPK, which also mediate the signalling activated by growth factors and play a role in the regulation of critical processes including cell proliferation, metabolism, apoptosis and angiogenesis. Inhibitors of PI3K, Akt and mTOR have been shown to sensitize selected tumor cells to cytotoxic drugs through multiple downstream effects. Moreover, the MAPK pathway, also implicated in the regulation of gene expression in response to stress stimuli, can interfere with the chemotherapy-induced proapoptotic signals. Targeting Hsp90, which acts as a molecular chaperone for survival factors including Akt, may have the potential advantage to simultaneously block multiple oncogenic pathways. Overall, the available evidence supports the interest of rationally designed approaches to enhance the efficacy of conventional antitumor treatments through the inhibition of survival pathways and the notion that the concomitant targeting of multiple pathways may be a successful strategy to deal with tumor heterogeneity and to overcome drug resistance of tumor cells.
journal_name
Biochem Pharmacoljournal_title
Biochemical pharmacologyauthors
Perego P,Cossa G,Zuco V,Zunino Fdoi
10.1016/j.bcp.2010.07.030subject
Has Abstractpub_date
2010-11-15 00:00:00pages
1459-65issue
10eissn
0006-2952issn
1873-2968pii
S0006-2952(10)00568-Xjournal_volume
80pub_type
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journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(93)90553-9
更新日期:1993-08-17 00:00:00
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journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(86)90246-7
更新日期:1986-03-01 00:00:00
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journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(99)00152-5
更新日期:1999-09-01 00:00:00
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journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(82)90293-3
更新日期:1982-12-01 00:00:00
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pub_type: 杂志文章
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更新日期:1993-02-09 00:00:00
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journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(93)90009-l
更新日期:1993-05-25 00:00:00
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journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(88)90062-7
更新日期:1988-10-15 00:00:00
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journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2006.08.009
更新日期:2006-11-15 00:00:00
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journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(94)90123-6
更新日期:1994-02-11 00:00:00
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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
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journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(88)90302-4
更新日期:1988-08-15 00:00:00
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journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(00)00235-5
更新日期:2000-05-01 00:00:00
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journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(95)00236-s
更新日期:1995-09-28 00:00:00
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journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2005.07.019
更新日期:2005-12-05 00:00:00
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journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(03)00553-7
更新日期:2003-11-15 00:00:00
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journal_title:Biochemical pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.bcp.2020.113959
更新日期:2020-07-01 00:00:00
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journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2009.05.026
更新日期:2009-09-15 00:00:00
abstract::The present study has examined the effect of colchicine and cytochalasin B, two cytoskeleton disrupter compounds, on the formation of dopamine in slices of rat renal cortex loaded with exogenous L-3,4-dihydroxyphenylalanine (L-DOPA); the deamination of newly formed dopamine into 3,4-dihydroxyphenylacetic acid (DOPAC) ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(92)90085-w
更新日期:1992-11-03 00:00:00
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journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(90)90277-r
更新日期:1990-03-15 00:00:00
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journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2019.08.011
更新日期:2019-11-01 00:00:00
abstract::It is increasingly clear that some of the effects of both free and derivatised long chain fatty acids in pancreatic beta-cells are mediated by a group of G-protein coupled receptors. Some of these display close structural homology while others are more divergent. This Commentary reviews the expression and functional r...
journal_title:Biochemical pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.bcp.2009.07.020
更新日期:2009-12-15 00:00:00
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journal_title:Biochemical pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.bcp.2019.02.033
更新日期:2019-07-01 00:00:00
abstract::Nuclear factor-kappaB (NF-kappaB) activity affects cell survival and determines the sensitivity of cancer cells to cytotoxic agents as well as to ionizing radiation. Preventing the protective function of NF-kappaB may result in chemo- and radio-sensitization of cancer cells. Therefore, NF-kappaB has emerged as one of ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章,评审
doi:10.1016/s0006-2952(98)00224-x
更新日期:1999-01-01 00:00:00
abstract::The 3'-fluoro-and 3'-azido-substituted derivatives of 2',3'-dideoxythymidine (ddThd), 2',3'-dideoxyuridine (ddUrd), 2',3'-dideoxy-5-ethyluridine (ddEtUrd) and 2',3'-dideoxycytidine (ddCyd) have been synthesized and evaluated for their anti-retrovirus activity [against human immunodeficiency virus (HIV) and murine Molo...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(88)90049-4
更新日期:1988-07-15 00:00:00
abstract::The levels and subcellular distribution of enzymes involved in defenses against reactive oxygen superoxide dismutase (SOD; E.C.1.15.1.1), glutathione peroxidase (GPX; E.C.1.11.1.9), catalase (CAT; E.C.1.11.1.6), and DT-diaphorase (DT; E.C.1.6.99.2) and of the conjugating enzymes glutathione transferase (GST; E.C.2.5.1...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(99)00185-9
更新日期:1999-10-15 00:00:00
abstract::No doubt can remain that the flavonoids have profound effects on the function of immune and inflammatory cells as determined by a large number and variety of in vitro and some in vivo observations. That these ubiquitous dietary chemicals may have significant in vivo effects on homeostasis within the immune system and ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章,评审
doi:10.1016/0006-2952(92)90489-6
更新日期:1992-03-17 00:00:00
abstract::Idiopathic pulmonary fibrosis (IPF) involves infiltration of leucocytes, pulmonary injury, fibrosis and resulting pulmonary dysfunction. Myofibroblasts and transforming growth factor (TGF)-beta1 have been suggested to play a major role in the pathology and the myofibroblasts are derived from both lung epithelial cells...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2010.05.025
更新日期:2010-09-15 00:00:00
abstract::We have previously shown [8] that rat liver adenosine kinase can produce [14C]AMP from [14C]adenosine (Ado) and unlabelled adenosine monophosphate (AMP), in the absence of ATP, by an exchange reaction. In this study, we investigated whether Ado or AMP could be replaced in this exchange reaction by other nucleosides or...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(95)02033-0
更新日期:1995-11-09 00:00:00
abstract::HOE 731, a substituted thienoimidazole derivative, was studied on [14C] aminopyrine uptake and oxygen consumption in isolated rabbit gastric glands. HOE 731 caused a concentration-dependent inhibition of [14C]aminopyrine uptake during histamine and dbcAMP stimulation. The inhibition during dbcAMP stimulation was in ac...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(90)90360-w
更新日期:1990-10-15 00:00:00
abstract::Cancer metastasis is a major cause for cancer-related death and inhibiting cancer metastasis is an alternative way to treat cancer. Several lines of reported evidence suggest that NADPH oxidase 4 (NOX4) is a potential target for intervention of cancer metastasis, as the reactive oxygen species (ROS) generated by this ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2013.05.011
更新日期:2013-07-15 00:00:00