Cellular Resistance to Cancer Chemotherapy

Skovsgaard, Torben; Nielsen, Dorte; Maare, C.; Wassermann, Karsten

doi:10.1016/s0074-7696(08)62253-6

Cited by 32 publications

(15 citation statements)

References 363 publications

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“…Point mutations on topoisomerase II, either in the vicinity of the ATP-binding site or in close contact with the active site, and/or post-translational modifications (methylation, phosphorylation) resulting in decreased interaction of the drug with the enzyme and/or the DNA, yield resistant cells [36, 114 -117]. In some resistant cell lines, the resistance has been linked to differential expression of the two isoforms (h and i) of topoisomerase II, or with modified cellular distribution of the enzyme [98]. Topoisomerase I also modifies DNA topology and is necessary both for replication and transcription.…”

Section: Resistance To Cancer Chemotherapy Mediated By Target Alterationmentioning

confidence: 99%

“…Some mutated enzymes less sensitive to inhibition and thus generating less DNA cleavage have been purified and studied (for reviews, see refs [98,119] Thymidylate-synthase alteration. The major cellular target of 5-fluorouracyl (5-FU) is thymidilate synthase (TS).…”

Section: Resistance To Cancer Chemotherapy Mediated By Target Alterationmentioning

confidence: 99%

“…Some compounds (leucoverine, methotrexate, etc.) have been shown to revert resistance, and are under investigation as promotors of 5-FU cytotoxic effects [98].…”

Section: Resistance To Cancer Chemotherapy Mediated By Target Alterationmentioning

confidence: 99%

“…54,1998 Review Article 417 aracytidine monophosphate (CMP), and into aracytidine diphosphate and finally into aracytidine triphosphate which is the active form of the drug. The major mechanism of resistance consists in a decrease of the deoxycytidine kinase involved in the first step of phosphorylation [98]. Purine analogues such as the 6-mercaptopurine (6-MP) and the 6-thioguanine (6-TG) are first converted into monophosphate ribonucleosides by hypoxanthine guanine phosphoribosyl transferase (HGPRT) and then activated into deoxyribonucleotides.…”

Section: Resistance To Nucleoside Analogues Used In Cancer Chemotherapymentioning

confidence: 99%

“…Purine analogues such as the 6-mercaptopurine (6-MP) and the 6-thioguanine (6-TG) are first converted into monophosphate ribonucleosides by hypoxanthine guanine phosphoribosyl transferase (HGPRT) and then activated into deoxyribonucleotides. The inability of HGPRT to initiate activation results in resistance to these drugs [98].…”

Section: Resistance To Nucleoside Analogues Used In Cancer Chemotherapymentioning

confidence: 99%

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Mechanisms of resistance to xenobiotics in human therapy

Saves¹,

Masson²

1998

Cellular and Molecular Life Sciences (CMLS)

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Xenobiotic resistance is the major cause of failure in human therapies. Because of their serious clinical and economical consequences, resistance phenomena have been intensively studied in the case of antibacterial, anticancer, antipaludic and anti-human immunodeficiency virus-1 therapies. Beside pharmacological factors that can impede the action of the drugs, several cellular mechanisms of resistance have been described. Surprisingly, these mechanisms are conserved among bacteria, eucaryotic cells, parasites and viruses. The efficiency of drugs can be circumvented by alteration of the drug cellular concentration (altered influx, enhanced efflux or sequestration), detoxification, alteration of the drug target, nonactivation or inactivation of the drug, or by enhanced DNA repair.

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Section: Resistance To Cancer Chemotherapy Mediated By Target Alterationmentioning

confidence: 99%

Section: Resistance To Cancer Chemotherapy Mediated By Target Alterationmentioning

confidence: 99%

“…Some compounds (leucoverine, methotrexate, etc.) have been shown to revert resistance, and are under investigation as promotors of 5-FU cytotoxic effects [98].…”

Section: Resistance To Cancer Chemotherapy Mediated By Target Alterationmentioning

confidence: 99%

Section: Resistance To Nucleoside Analogues Used In Cancer Chemotherapymentioning

confidence: 99%

Section: Resistance To Nucleoside Analogues Used In Cancer Chemotherapymentioning

confidence: 99%

See 3 more Smart Citations

Mechanisms of resistance to xenobiotics in human therapy

Saves¹,

Masson²

1998

Cellular and Molecular Life Sciences (CMLS)

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Proteomic analysis of multidrug‐resistance mechanisms in adriamycin‐resistant variants of DLKP, a squamous lung cancer cell line

et al. 2009

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Alterations in protein expression associated with adriamycin resistance in a panel of variants derived from the poorly differentiated squamous cell lung carcinoma DLKP were investigated using 2-D DIGE. Of the 80 proteins identified as being differentially expressed, 32 correlated to adriamycin resistance. Twenty-four proteins showed positive correlations with drug resistance, 11 correlated directly with increase in the resistance (including NDPK, RPA2, CCT2, HSP70 and Annexin A1) while 13 proteins (including HNRP K and H1, aldehyde dehydrogenase (ALDH), stomatin and CCT3) increased to a similar level in all drug-resistant variants. Fewer proteins showed an inverse correlation with resistance; two (protein disulphide isomerase (PDI) and HSP70 variant 1) displayed a similar decrease in all variants and six (including prohibitin (PHB) and EIF5A) correlated inversely with resistance. Three proteins (EEF1D, Actin G1 and Annexin 1) correlated with the invasive status of these variants. Some expected targets of adriamycin action showed correlation with resistance including RPA2 (critical for DNA damage repair), while others proteins involved in protection from ROS production (such as GST, peroxiredoxins and thioredoxins) did not. The proteomic analysis revealed a large number of changes in protein expression that may contribute to a more apoptosis-resistant state. Many of these changes could provide novel targets for overcoming resistance.

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Doxorubicin‐Loaded Polymeric Micelle Overcomes Multidrug Resistance of Cancer by Double‐Targeting Folate Receptor and Early Endosomal pH

Kim

Lee

et al. 2008

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An optimized, pH-sensitive mixed micelle system conjugated with folic acid was prepared to challenge multidrug resistance (MDR) in cancers. The micelles were composed of poly(histidine (His)-co-phenylalanine (Phe))-b-poly(ethylene glycol) (PEG) and poly(L-lactic acid) (PLLA)-b-PEG-folate. Core-forming, pH-sensitive hydrophobic blocks of poly(His-co-Phe) of varying composition were synthesized. The composition-dependent pK values of poly(His-co-Phe) (Mn=5,000−5,500 Da) were examined. The size and critical micelle concentration were evaluated as a function of pH. The pH sensitivity of the micelles was roughly controlled by the copolymer composition, and its fine tuning to early endosomal pH was achieved by blending PLLA(3K)-b-PEG (2K)-folate, especially in the presence of a basic anticancer drug, doxorubicin (DOX).To prove the efficacy of the micellar system, in vitro tests including cell viability, folate receptormediated endocytosis, and endosomolytic acitivity were conducted against both wild-type (A2780) and DOX-resistant ovarian carcinoma cell lines (A2780/DOX R ). From the physicochemical properties and in vitro results, a mixed micelle system composed of poly(His-co-Phe (16 mole%))-b-PEG (80 wt%) and PLLA-b-PEG-folate (20 wt%) was selected to target early endosomal pH. DOXloaded (ca. 20 wt%) micelles effectively killed both wild-type sensitive and MDR cancer cell lines through an instantaneous high dose of DOX in the cytosol, resulting from active internalization, accelerated DOX release triggered by endosomal pH, and a disruption of endosomal pH.

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Cellular Resistance to Cancer Chemotherapy

Cited by 32 publications

References 363 publications

Mechanisms of resistance to xenobiotics in human therapy

Mechanisms of resistance to xenobiotics in human therapy

Proteomic analysis of multidrug‐resistance mechanisms in adriamycin‐resistant variants of DLKP, a squamous lung cancer cell line

Doxorubicin‐Loaded Polymeric Micelle Overcomes Multidrug Resistance of Cancer by Double‐Targeting Folate Receptor and Early Endosomal pH

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