Chemotherapy-induced resistance by ATP-binding cassette transporter genes

Gillet, Jean‐Pierre; Efferth, Thomas; Remacle, José

doi:10.1016/j.bbcan.2007.05.002

Cited by 218 publications

(246 citation statements)

References 339 publications

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“…One of the major, extensively studied mechanisms of chemoresistance, is the overexpression of several ATP-dependent drug efflux pumps (Gillet et al, 2007). In NB as well, high levels of MDR1 mRNA are often associated with acquired resistance to chemotherapy (Goldstein et al, 1990) and thus poor survival of the patients.…”

Section: Discussionmentioning

confidence: 99%

The Wnt receptor FZD1 mediates chemoresistance in neuroblastoma through activation of the Wnt/β-catenin pathway

et al. 2009

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The development of chemoresistance represents a major obstacle in the successful treatment of cancers such as neuroblastoma (NB), a particularly aggressive childhood solid tumour. The mechanisms underlying the chemoresistant phenotype in NB were addressed by gene expression profiling of two doxorubicin (DoxR)-resistant vs sensitive parental cell lines. Not surprisingly, the MDR1 gene was included in the identified upregulated genes, although the highest overexpressed transcript in both cell lines was the frizzled-1 Wnt receptor (FZD1) gene, an essential component of the Wnt/b-catenin pathway. FZD1 upregulation in resistant variants was shown to mediate sustained activation of the Wnt/b-catenin pathway as revealed by nuclear b-catenin translocation and target genes transactivation. Interestingly, specific microadapted short hairpin RNA (shRNAmir)-mediated FZD1 silencing induced parallel strong decrease in the expression of MDR1, another b-catenin target gene, revealing a complex, Wnt/b-catenin-mediated implication of FZD1 in chemoresistance. The significant restoration of drug sensitivity in FZD1-silenced cells confirmed the FZD1-associated chemoresistance. RNA samples from 21 patient tumours (diagnosis and postchemotherapy), showed a highly significant FZD1 and/or MDR1 overexpression after treatment, underlining a role for FZD1-mediated Wnt/b-catenin pathway in clinical chemoresistance. Our data represent the first implication of the Wnt/b-catenin pathway in NB chemoresistance and identify potential new targets to treat aggressive and resistant NB.

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Section: Discussionmentioning

confidence: 99%

The Wnt receptor FZD1 mediates chemoresistance in neuroblastoma through activation of the Wnt/β-catenin pathway

et al. 2009

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“…ABC transporters 'pump' drugs, such as anti-neoplastic drugs, out of the cells against a concentration gradient, this is the basic mechanism of chemoresistance (10). To date, 48 members of the ABC transporter family have been isolated and identified (11,12). However, not all ABC family members are reported to participate in chemoresistance, Dean and Annilo (13) indicated that only ABCA2, ABCB1, ABCC1, ABCC3 and ABCG2 were proven to play crucial roles in the development of drug resistance.…”

Section: Introductionmentioning

confidence: 99%

NF-κB signaling plays irreplaceable roles in cisplatin-induced bladder cancer chemoresistance and tumor progression

Sun

Guan

Liang

et al. 2015

International Journal of Oncology

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Abstract. Bladder cancer (BCa) is the most vital urogenital malignant disease worldwide, bringing huge economic and social burden every year. Clinically, BCa is subdivided into superficial type and invasive type according to clinicpathology, accompanied with different strategy of therapy. Number of reports indicate that 10-30% of superficial BCa will inevitable progress into invasive type, manifesting enhanced malignant behavior compared to original invasive type. Regardless of the original being an original invasive type or invasive type that progressed from superficial type of BCa, chemotherapy (including adjuvant or neo-adjuvant chemotherapy) in line with radiotherapy is the final regimen for BCa patients. Previous reports pointed out the high efficiency of cisplatin-containing chemotherapeutic regimen for BCa patients, leading to wide use of this regimen in BCa therapeutics. However, cisplatin-resistance inevitably appear, resulting in the failure of the BCa chemotherapy, the mechanism of which is still unknown. In the present study, parental BCa cell lines T24/J82 were used to obtain stable-cisplatinresistance cell lines T24 R /J82 R , which showed enhanced capacity of malignancy, tumorigenesis and drug resistance, accompanied by elevated expression of EMT markers. The further mechanism investigation suggested that prolonged time of cisplatin-treatment contributed to the activation of the NF-κB signal, resulting in the upregulation of EMT markers, the maintenance of stem cell marker and the elevated expression of ABCB1. Thus, our study provides us a new view of the role of NF-κB signaling in BCa therapeutics.

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“…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). Although the roles of 13 ABC transporters in MDR have been fully characterized, recent studies suggest the involvement of up to 30 members of the 48 encoded in the human genome (16,17).…”

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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.

387

319

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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.

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Chemotherapy-induced resistance by ATP-binding cassette transporter genes

Cited by 218 publications

References 339 publications

The Wnt receptor FZD1 mediates chemoresistance in neuroblastoma through activation of the Wnt/β-catenin pathway

The Wnt receptor FZD1 mediates chemoresistance in neuroblastoma through activation of the Wnt/β-catenin pathway

NF-κB signaling plays irreplaceable roles in cisplatin-induced bladder cancer chemoresistance and tumor progression

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

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