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
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Journal ArticleDOI
Human ATP-binding cassette transporters ABCB1 and ABCG2 confer resistance to histone deacetylase 6 inhibitor ricolinostat (ACY-1215) in cancer cell lines.
Chung-Pu Wu,Ya-Ju Hsieh,Megumi Murakami,Shahrooz Vahedi,Sung-Han Hsiao,Ni Yeh,An-Wei Chou,Yan-Qing Li,Yu-Shan Wu,Jau-Song Yu,Suresh V. Ambudkar +10 more
TL;DR: It is suggested that co‐administration of ricolinostat with a modulator of ABCB1 or ABCG2 could overcome ricolinstat resistance in human cancer cells, which may be relevant to its use in the clinic.
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TL;DR: This editorial highlights the importance of targeted nanosystems against CRC, including nanoconjugates of monoclonal antibodies (mAbs) along with drugs and organic/inorganic nanoparticles.
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Reduced chemotherapy sensitivity in EGFR-mutant lung cancer patient with frontline EGFR tyrosine kinase inhibitor
Zhu Zeng,Zhu Zeng,Hong-Hong Yan,Xu-Chao Zhang,Wen-Zhao Zhong,Yan-yan He,Jin-lin Guan,Fei-Yu Niu,Zhi Xie,Yi-Sheng Huang,Chong-Rui Xu,Song Dong,Yi-Long Wu +12 more
TL;DR: In EGfr-mutant patients, frontline EGFR-TKI significantly reduced the sensitivity of subsequent chemotherapy compared with that of TKI-naïve frontline chemotherapy.
Journal ArticleDOI
Positron Emission Tomography Diagnostic Imaging in Multidrug-Resistant Hepatocellular Carcinoma: Focus on 2-Deoxy-2-(18F)Fluoro-d-Glucose
TL;DR: The relationship between MDR expression in HCC, and [18F]FDG uptake by tumor cells is summed up, showing that this radiopharmaceutical may provide a useful tool for the study of chemoresistance in H CC, and that the use of this marker may contribute to the therapeutic choice on this highly aggressive tumor.
Journal ArticleDOI
Efflux Pumps Modulation in Colorectal Adenocarcinoma Cell Lines: The Role of Nuclear Medicine
João Casalta-Lopes,Ana M. Abrantes,Mafalda Laranjo,J. Rio,Bárbara Oliveiros,Ana Bela Sarmento-Ribeiro,Maria Filomena Botelho +6 more
TL;DR: This study aims to compare 99mTc-Sestamibi transport kinetics in human colorectal adenocarcinoma cell lines, in the presence and absence of the MDR modulators verapamil and BSO.
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.