Abstract:
:Platinum-based chemotherapeutics are the mainstay of treatment of a range of tumors achieving high response rates but limited in the course of disease by appearance of drug resistance. Tumor cells respond with reduced uptake and increased intracellular inactivation of the drugs, as well as increased DNA repair and general resistance to chemotherapyinduced cell death. Cisplatin is known to induce expression of cyclophilins, a group of proteins that have peptidyl-prolyl cis-trans isomerase (PPIase) and molecular chaperone activities, as stress response. Cyclophilin A (CypA) and other members of this family are inhibited by cyclosporin A (CsA) which sensitized diverse drug-resistant tumor cell lines in vitro to cisplatin. This effect of CsA was attributed to metabolic changes, inhibition of DNA repair, enhancement of apoptosis, altered intracellular signal transduction or increased production of reactive oxygen species (ROS), although no definitive explanation was provided so far. Several clinical trials employing cisplatin/carboplatin in combination with CsA yielded unsatisfactory results. Since viral replication was found to be dependent on cyclophilins of the host cells, effective new inhibitors, different from CsA or with low or absent immunosuppressive activity, are in development or clinical trials. Sanglifehrins are more potent than CsA and proved to increase toxicity of cisplatin against hepatocellular cancer cells in vitro. These novel cyclophilin inhibitors may offer new opportunities to achieve reversal of resistance to platinumbased drugs in refractory patients. Responsive cancer patients may be enriched in clinical trials by an identification of the downstream targets of Cyps responsible for chemoresistance.
journal_name
Curr Cancer Drug Targetsjournal_title
Current cancer drug targetsauthors
Hamilton Gdoi
10.2174/15680096113136660109subject
Has Abstractpub_date
2014-01-01 00:00:00pages
46-58issue
1eissn
1568-0096issn
1873-5576pii
CCDT-EPUB-57194journal_volume
14pub_type
杂志文章,评审abstract::One of the challenges of cancer therapeutics is to discover targets unique to the tumor cell population. Constitutively activated tyrosine kinases play a role in the malignant phenotype in a number of different cancers. While the kinases may be present in the normal cell, the cancer cell is often dependent upon the ac...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/156800906779010209
更新日期:2006-12-01 00:00:00
abstract::Copper is a trace element which is tightly regulated in mammals and lower animals. Disruptions of copper homeostasis in humans are rare and they cause serious disorders such as Wilson's disease and Menke's disease. Copper plays an important role in promoting physiological and malignant angiogenesis. Formation of new b...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/156800905774574066
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abstract::Cisplatin is one of the most commonly used drugs in the treatment of gastric cancer. However, drug resistance is a major obstacle for effective treatment and originates in multiple mechanisms such as enhanced DNA repair and anti-apoptosis. Our previous results demonstrated that XRCC1 was a key regulator of cisplatin i...
journal_title:Current cancer drug targets
pub_type: 杂志文章
doi:10.2174/1568009614666141028094612
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abstract:BACKGROUND:CYP1B1 is recognized as a valuable target for chemotherapy. It catalyzes the bioactivation of naphthoquinone oximes within certain cancer cell lines. However, the expression level of CYP1B1 in melanoma and the functional role regulating the activity of DMAKO-20 as a representative naphthoquinone oxime agains...
journal_title:Current cancer drug targets
pub_type: 杂志文章
doi:10.2174/1568009620666201116112937
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abstract::Polyisoprenylated proteins (PPs) methylation by polyisoprenylated protein methyl transferase (PPMTase) is counteracted by polyisoprenylated methylated protein methyl esterase (PMPMEase). This is the only reversible step of the polyisoprenylation pathway as the relative amounts of the acid and ester forms are determine...
journal_title:Current cancer drug targets
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journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
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journal_title:Current cancer drug targets
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journal_title:Current cancer drug targets
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doi:10.2174/1568009618666180629150927
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journal_title:Current cancer drug targets
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journal_title:Current cancer drug targets
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journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
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更新日期:2017-01-01 00:00:00
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journal_title:Current cancer drug targets
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journal_title:Current cancer drug targets
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更新日期:2004-03-01 00:00:00
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journal_title:Current cancer drug targets
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journal_title:Current cancer drug targets
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journal_title:Current cancer drug targets
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更新日期:2008-06-01 00:00:00
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journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/156800907780006869
更新日期:2007-02-01 00:00:00
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journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
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journal_title:Current cancer drug targets
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journal_title:Current cancer drug targets
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更新日期:2011-06-01 00:00:00
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journal_title:Current cancer drug targets
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更新日期:2016-01-01 00:00:00
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journal_title:Current cancer drug targets
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journal_title:Current cancer drug targets
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更新日期:2015-01-01 00:00:00
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journal_title:Current cancer drug targets
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journal_title:Current cancer drug targets
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更新日期:2010-12-01 00:00:00
abstract::The application of nanotechnology to biomedical research is expected to have a major impact leading to the development of new types of diagnostic and therapeutic tools. One focus in nanobiotechnology is to develop safe and efficient drug/gene delivery vehicles. Research into the rational delivery and targeting of phar...
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更新日期:2011-02-01 00:00:00
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journal_title:Current cancer drug targets
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更新日期:2004-06-01 00:00:00
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journal_title:Current cancer drug targets
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更新日期:2007-09-01 00:00:00
abstract::Targets for cancer therapy are conventionally selected by identification of molecules acting downstream of established tumour suppressors and oncoproteins, such as p53, c-Myc and Ras. However, the forward genetics approach provides an alternative, conceptually distinct, strategy for identifying target molecules de nov...
journal_title:Current cancer drug targets
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更新日期:2013-01-01 00:00:00