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
Expression of the multidrug transporter P-glycoprotein is inversely related to that of apoptosis-associated endogenous TRAIL.
Paloma Silva de Souza,James P. Madigan,Jean-Pierre Gillet,Khyati Kapoor,Suresh V. Ambudkar,Raquel Ciuvalschi Maia,Michael M. Gottesman,King Leung Fung +7 more
TL;DR: It is found that using doxycycline to control Pgp expression has a significant advantage over tetracycline, in that doxy cycline caused less endogenous gene expression modification/perturbation, and was more potent than tetrACYcline in suppressing PGP expression.
Journal ArticleDOI
Co-delivery of synergistic antioxidants from food sources for the prevention of oxidative stress
Erika Fleming,Yangchao Luo +1 more
TL;DR: The potential benefits and challenges of co-delivering both hydrophilic and hydrophobic natural antioxidants within the same NDS for a shift from mono-encapsulation to co-Encapsulation for optimal antioxidant activity are reviewed.
Journal ArticleDOI
Ginsenoside Rg5 overcomes chemotherapeutic multidrug resistance mediated by ABCB1 transporter: in vitro and in vivo study.
Sen-Ling Feng,Hai-Bin Luo,Liang Cai,Jie Zhang,Dan Wang,Ying-Jiang Chen,Huan-Xing Zhan,Zhi-Hong Jiang,Zhi-Hong Jiang,Ying Xie +9 more
TL;DR: In nude mice bearing A549/T tumor, Rg5 and TXT treatment significantly suppressed the growth of drug-resistant tumors without increase in toxicity when compared to TXT given alone at same dose.
Journal ArticleDOI
Characterizing binding of small molecules. II. Evaluating the potency of small molecules to combat resistance based on docking structures
TL;DR: The MIEC-SVM method is able to predict resistant profiles for new drugs based on the docking structures as indicated by its satisfactory performance in leave-one-drug-out and leave-drug/mutants-out tests and can also facilitate designing effective therapeutic combinations by combining drugs with complementary resistant profiles.
Journal ArticleDOI
Nanomedicine to overcome cancer multidrug resistance.
TL;DR: This review mainly focuses on some pivotal strategies to combat Multidrug resistance, including the enhanced permeability and retention (EPR) effect, stealth nanoparticles to prolong circulation time, endosomal escape, active drug delivery, stimuli sensitive drug release, and targeted co-delivery of different compounds.
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.