Book ChapterDOI
Mechanisms of multidrug resistance in cancer.
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TLDR
Identifying genes and mechanisms critical to the development of MDR in vivo and establishing a reliable method for analyzing clinical samples could help to predict theDevelopment of resistance and lead to treatments designed to circumvent it.Abstract:
The development of multidrug resistance (MDR) to chemotherapy remains a major challenge in the treatment of cancer. Resistance exists against every effective anticancer drug and can develop by numerous mechanisms including decreased drug uptake, increased drug efflux, activation of detoxifying systems, activation of DNA repair mechanisms, evasion of drug-induced apoptosis, etc. In the first part of this chapter, we briefly summarize the current knowledge on individual cellular mechanisms responsible for MDR, with a special emphasis on ATP-binding cassette transporters, perhaps the main theme of this textbook. Although extensive work has been done to characterize MDR mechanisms in vitro, the translation of this knowledge to the clinic has not been crowned with success. Therefore, identifying genes and mechanisms critical to the development of MDR in vivo and establishing a reliable method for analyzing clinical samples could help to predict the development of resistance and lead to treatments designed to circumvent it. Our thoughts about translational research needed to achieve significant progress in the understanding of this complex phenomenon are therefore discussed in a third section. The pleotropic response of cancer cells to chemotherapy is summarized in a concluding diagram.read more
Citations
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Journal ArticleDOI
Reliability of tumor primary cultures as a model for drug response prediction: expression profiles comparison of tissues versus primary cultures from colorectal cancer patients
TL;DR: Response of primary tumor cells toward different drugs is not linearly associated to tumor tissues, and it is found that primary cultures may have increased susceptibility toward paclitaxel, but reduced susceptibility toward analogues of fluorouracil compared with original tumors.
Journal ArticleDOI
Ailanthone reverses multidrug resistance by inhibiting the P-glycoprotein-mediated efflux in resistant K562/A02 cells.
TL;DR: In this study, ailanthone (AIL), a natural compound extracted from the whole seedlings of Ailanthus altissima was shown to mediate the reversal of P-GLP-induced MDR and restore the susceptibility of K562/A02 cells to doxorubicin (DOX).
Journal ArticleDOI
Structural elucidation and chemical characterization of underutilized fruit silverberry (Elaeagnus pyriformis) silver nanoparticles playing a dual role as anti-cancer agent by promoting apoptosis and inhibiting ABC transporters
Swarnendra Banerjee,Pallab Kar,Indrani Sarkar,Abhijit Chhetri,Dipu Kumar Mishra,Ankita Dutta,Anoop Kumar,Biswajit Sinha,Arnab Sen +8 more
TL;DR: In this article, the synthesis of silver nanoparticles (AgNP) from silver nitrate (AgNO3) using the underutilized fruit of Elaeagnus pyriformis fruit juice in an optimized reaction.
Journal ArticleDOI
Advances of proteomics technologies for multidrug-resistant mechanisms
TL;DR: The recent developments and progresses by comparative proteomic approaches to identify potential MDR mechanisms in drug-selected model cancer cell lines are reviewed to help understand and design chemical sensitizers.
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Advances in Hydrogel-Based Microfluidic Blood–Brain-Barrier Models in Oncology Research
TL;DR: Recent advancements in BBB-on-chip models targeting brain malignancies are presented and the utility of hydrogel-based BBB models that could further strengthen the future application of microfluidic devices in oncology research are examined.
References
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Journal ArticleDOI
ONCOMINE: A Cancer Microarray Database and Integrated Data-Mining Platform
Daniel R. Rhodes,Jianjun Yu,K. Shanker,Nandan P. Deshpande,Radhika Varambally,Debashis Ghosh,Terrence R. Barrette,Akhilesh Pandey,Arul M. Chinnaiyan +8 more
TL;DR: ONCOMINE is presented, a cancer microarray database and web-based data-mining platform aimed at facilitating discovery from genome-wide expression analyses and novel biomarkers and therapeutic targets are discovered.
Journal ArticleDOI
A surface glycoprotein modulating drug permeability in Chinese hamster ovary cell mutants.
TL;DR: Observations on the molecular basis of pleiotropic drug resistance are interpreted in terms of a model wherein certain surface glycoproteins control drug permeation by modulating the properties of hydrophobic membrane regions.
Journal ArticleDOI
Targeting multidrug resistance in cancer
Gergely Szakács,Jill K. Paterson,Joseph A. Ludwig,Catherine Booth-Genthe,Michael M. Gottesman +4 more
TL;DR: Various approaches to combating multidrug-resistant cancer are described, including the development of drugs that engage, evade or exploit efflux by ABC transporters.
Journal ArticleDOI
Overexpression of a transporter gene in a multidrug-resistant human lung cancer cell line
Susan P.C. Cole,Gabu Bhardwaj,James H. Gerlach,J. E. Mackie,Caroline E. Grant,Kurt C. Almquist,Alistair J. Stewart,Ebba U. Kurz,A. M. V. Duncan,Roger G. Deeley +9 more
TL;DR: Reversion to drug sensitivity was associated with loss of gene amplification and a marked decrease in mRNA expression, and the mRNA encodes a member of the ATP-binding cassette transmembrane transporter superfamily.
Journal ArticleDOI
A "Silent" Polymorphism in the MDR1 Gene Changes Substrate Specificity
Chava Kimchi-Sarfaty,Jung Mi Oh,In-Wha Kim,Zuben E. Sauna,Anna Maria Calcagno,Suresh V. Ambudkar,Michael M. Gottesman +6 more
TL;DR: It is hypothesized that the presence of a rare codon, marked by the synonymous polymorphism, affects the timing of cotranslational folding and insertion of P-gp into the membrane, thereby altering the structure of substrate and inhibitor interaction sites.