Mechanisms of Multidrug Resistance in Cancer

Gillet, Jean‐Pierre; Gottesman, Michael M.

doi:10.1007/978-1-60761-416-6_4

Cited by 604 publications

(479 citation statements)

References 216 publications

Supporting

Mentioning

468

Contrasting

Unclassified

Order By: Relevance

“…Over the past 30 y, in vitro studies have led to the enumeration of close to 400 genes whose expression affects response to chemotherapy (13). Among those genes, ATP-binding cassette (ABC) transporters, a superfamily of 48 highly homologous members classified in seven subfamilies, have an important role in the pleiotropic mechanisms mediating MDR by exporting chemotherapeutic agents from the cell (14,15).…”

mentioning

confidence: 99%

Redefining the relevance of established cancer cell lines to the study of mechanisms of clinical anti-cancer drug resistance

Gillet

Calcagno

Varma

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

405

322

View full text Add to dashboard Cite

Although in vitro models have been a cornerstone of anti-cancer drug development, their direct applicability to clinical cancer research has been uncertain. Using a state-of-the-art Taqman-based quantitative RT-PCR assay, we investigated the multidrug resistance (MDR) transcriptome of six cancer types, in established cancer cell lines (grown in monolayer, 3D scaffold, or in xenograft) and clinical samples, either containing >75% tumor cells or microdissected. The MDR transcriptome was determined a priori based on an extensive curation of the literature published during the last three decades, which led to the enumeration of 380 genes. No correlation was found between clinical samples and established cancer cell lines. As expected, we found up-regulation of genes that would facilitate survival across all cultured cancer cell lines evaluated. More troubling, however, were data showing that all of the cell lines, grown either in vitro or in vivo, bear more resemblance to each other, regardless of the tissue of origin, than to the clinical samples they are supposed to model. Although cultured cells can be used to study many aspects of cancer biology and response of cells to drugs, this study emphasizes the necessity for new in vitro cancer models and the use of primary tumor models in which gene expression can be manipulated and small molecules tested in a setting that more closely mimics the in vivo cancer microenvironment so as to avoid radical changes in gene expression profiles brought on by extended periods of cell culture.

show abstract

mentioning

confidence: 99%

Redefining the relevance of established cancer cell lines to the study of mechanisms of clinical anti-cancer drug resistance

Gillet

Calcagno

Varma

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

405

322

View full text Add to dashboard Cite

show abstract

“…It is suggested that different tumor cell types have their own unique mechanisms leading to MDR (Gillet and Gottesman, 2010;Al-Lazikani et al, 2012). The association between GST and tumors was initially reported by Wang (Wang and Few, 1985).…”

Section: Discussionmentioning

confidence: 93%

Roles of GST-π and polβ Genes in Chemoresistance of Esophageal Carcinoma Cells

Tang

Xing²,

Li³

et al. 2013

Asian Pacific Journal of Cancer Prevention

View full text Add to dashboard Cite

“…Genetic and molecular studies have shown that most of the malignant cancer cells have amplified multi drug resistance (MDR) 1 and multidrug resistance associated protein (MRP) genes, which are the members of ATP-binding cassette transporter (ABC transporter) superfamily. 97 Now, a series of studies dictate that tumor derived exosomes added the layer of complexity in the complex nature of cancer by transmission of resistance from resistant cells to sensitive ones (Figure 1). Bebawy et al, showed the transmission of functional P-glycoprotein (P-gp) (MDR1) from drug resistant cancer cells (VLB 100 ) to drug sensitive cancer cells (CCRF-CEM) over a co-culture period of 4 hours.…”

Section: Role In Drug Resistancementioning

confidence: 99%

Exosomes: Emerging Players of Intercellular Communication in Tumor Microenvironment

et al. 2014

View full text Add to dashboard Cite

Seminal discoveries have established the role of complex tumor microenvironment (TME) in cancer progression; and later on also uncovered that vesiculation is an integral part of intercellular communication among various cell types in coordinating the tumor assembly in a dynamic manner. Exosomes are small membrane bound endosomal vesicles, which are classically known for their role in discarding cellular wastes; however, recent reports underlined their novel role in malignancy by their release from cells into the TME. Since then, the role of exosomes have been a subject of increasing interest, as exosome mediated intercellular communications offer a novel reciprocal relationship between cancer and stromal cells within the TME and modulate the fate and function of the recipient cells to finally shape the tumor progression. Exosomes are characterised by different features including size, content and mode of delivery; and its cargo delivers interesting bioactive components in the form of proteins, miRNAs or other molecules to the target cell. In the pursuit of further study of exosomes, it was found that with the help of its distinct bioactive components, exosomes specifically regulate tumor growth, angiogenesis, metastasis as well as drug resistance properties. In fact, it acts as a bridge between different signaling networks, present inside the spatially distant cells of the heterogeneous tumor population. In the current endeavour, we have highlighted the role of exosomes in modulating the intercellular crosstalk during tumor growth and progression, and proposed certain novel roles of exosomes to address the few enigmatic questions of cancer cell biology. Keywords:Exosome, Tumor Microenvironment, Angiogenesis, Metastasis, Drug Resistance Abbreviations:Extracellular vesicles (EV); Tumor Microenvironment (TME); Carcinoma-associated fibroblasts (CAFs); Tumor-associated macrophages (TAM); Transforming growth factor-beta (TGF-β); Vascular endothelial growth factor (VEGF); Endothelial cell (EC); Matrix metalloproteinases (MMPs); Heat shock proteins (HSPs); Cancer stem cells (CSCs); Microvesicles (MVs); Epithelial-mesenchymal transition (EMT); Multi drug resistance-1 (MDR-1); Multidrug resistance associated protein (MRP); ATP-binding cassette transporter (ABC transporter) DISCOVERIES 2014, Jul-Sep, 2(3): e26 DOI: 10.15190/d.2014.18 Exosome mediated intercellular crosstalk in TME www.discoveriesjournals.org 2 ♦ Exosomes comprise of bioactive components such as proteins, RNAs, miRNAs or lipids, and play a pivotal role in modulating tumor niche by controlling intercellular crosstalk.♦ Exosomes mediated intercellular communications and signals within TME regulate tumor growth, angiogenesis, metastasis and drug resistance.

show abstract

Mechanisms of Multidrug Resistance in Cancer

Cited by 604 publications

References 216 publications

Redefining the relevance of established cancer cell lines to the study of mechanisms of clinical anti-cancer drug resistance

Redefining the relevance of established cancer cell lines to the study of mechanisms of clinical anti-cancer drug resistance

Roles of GST-π and polβ Genes in Chemoresistance of Esophageal Carcinoma Cells

Exosomes: Emerging Players of Intercellular Communication in Tumor Microenvironment

Contact Info

Product

Resources

About