Taxane resistance in breast cancer: A closed HER2 circuit?

Hoon, Joep P.J. de; Veeck, Jürgen; Vriens, B.E.P.J.; Calon, Tim George Ate; Engeland, Manon van; Tjan‐Heijnen, Vivianne C. G.

doi:10.1016/j.bbcan.2012.01.001

Cited by 27 publications

(41 citation statements)

References 133 publications

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“…HER2 signaling via NFkB is known to contribute to progression and chemoresistance in ovarian, 49-51 gastric, 52 and breast cancers. [53][54][55][56] In primary breast tumors, HER2 not only stimulates NFkB expression but is also itself unregulated by NFkB, stimulating a closed loop responsible for chemoresistance, which includes STAT3. [54][55][56] WLS may be another key component of this signaling pathway.…”

Section: Wls and Her2 In Gastric Ovarian And Breast Cancersmentioning

confidence: 99%

“…[53][54][55][56] In primary breast tumors, HER2 not only stimulates NFkB expression but is also itself unregulated by NFkB, stimulating a closed loop responsible for chemoresistance, which includes STAT3. [54][55][56] WLS may be another key component of this signaling pathway. In this way, WLS may act as a biomarker to identify patients who are unlikely to respond to chemotherapy and/or trastuzimab alone, and join HER2 analysis in the armamentarium of personalized medicine-related biomarkers.…”

Section: Wls and Her2 In Gastric Ovarian And Breast Cancersmentioning

confidence: 99%

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Analysis of wntless (WLS) expression in gastric, ovarian, and breast cancers reveals a strong association with HER2 overexpression

Stewart¹,

James

McCluggage

et al. 2015

Modern Pathology

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The oncogenic role of WNT is well characterized. Wntless (WLS) (also known as GPR177, or Evi), a key modulator of WNT protein secretion, was recently found to be highly overexpressed in malignant astrocytomas. We hypothesized that this molecule may be aberrantly expressed in other cancers known to possess aberrant WNT signaling such as ovarian, gastric, and breast cancers. Immunohistochemical analysis using a TMA platform revealed WLS overexpression in a subset of ovarian, gastric, and breast tumors; this overexpression was associated with poorer clinical outcomes in gastric cancer (P ¼ 0.025). In addition, a strong correlation was observed between WLS expression and human epidermal growth factor receptor 2 (HER2) overexpression. Indeed, 100% of HER2-positive intestinal gastric carcinomas, 100% of HER2-positive serous ovarian carcinomas, and 64% of HER2-positive breast carcinomas coexpressed WLS protein. Although HER2 protein expression or gene amplification is an established predictive biomarker for trastuzumab response in breast and gastric cancers, a significant proportion of HER2-positive tumors display resistance to trastuzumab, which may be in part explainable by a possible mechanistic link between WLS and HER2. Modern Pathology (2015) 28, 428-436; doi:10.1038/modpathol.2014 published online 26 September 2014 The molecular mechanisms controlling the maturation and secretion of WNT proteins in the cells responsible for their production are attracting considerable attention. Wntless (WLS) (also known as GPR177 and Evi) was recently discovered as a key modulator of WNT protein secretion. [1][2][3] This multipass transmembrane protein localizes to compartments of the secretory pathway including the Golgi apparatus, endosomes, and plasma membrane. WLS acts as a WNT cargo receptor, shuttling palmitoylated Wnts from the endoplasmic reticulum to the plasma membrane, and it is required for exocytosis of WNT proteins from the WNT-producing cells. 4 In contrast to most other components of the WNT signaling pathway, only a single WLS gene exists in vertebrate genomes. WLS appears to be required for the secretion of all WNT proteins in both the canonical and noncanonical WNT pathways. 5 Augustin et al 6 recently demonstrated that WLS is highly overexpressed in malignant astrocytomas, indicating that the aberrant release of canonical and noncanonical WNT is a potential driver of glioma tumorigenesis required for proliferation, survival, and migration of glioma cells. Their work raises the question of whether WLS has a similar role in other cancers known to have aberrant activation of WNT signaling, including ovarian, gastric, and breast cancers. [7][8][9][10][11][12][13][14][15]

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Section: Wls and Her2 In Gastric Ovarian And Breast Cancersmentioning

confidence: 99%

Section: Wls and Her2 In Gastric Ovarian And Breast Cancersmentioning

confidence: 99%

Analysis of wntless (WLS) expression in gastric, ovarian, and breast cancers reveals a strong association with HER2 overexpression

Stewart¹,

James

McCluggage

et al. 2015

Modern Pathology

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“…After treatment with the mixture of free DOX and PTX (DOX+PTX) with total drug concentration of 1 μg/mL, only slight apoptosis took place in KBv cells, which is consistent with the studies reporting that DOX and PTX are the substrates of P-gp, multidrug resistance-associated protein, and breast cancer-resistant protein. 41,[43][44][45] In contrast, after 24-hour treatment, the cell nuclei became severely fragmented and segmented into dense nuclear parts in the drug-loaded Pluronic polymeric micelles group. Compared with PF-DP, c(RGDyK)-FP-DP was found to induce more severe fragmentation of the cell nuclei as shown in Figure 7A.…”

Section: Cell Apoptosismentioning

confidence: 86%

Dual-functional c(RGDyK)-decorated Pluronic micelles designed for antiangiogenesis and the treatment of drug-resistant tumor

Chen¹,

Zhang²,

Huang³

et al. 2015

IJN

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Dual-functional drug delivery system was developed by decorating c(RGDyK) (cyclic RGD [arginine-glycine-aspartic acid] peptide) with Pluronic polymeric micelles (c[RGDyK]-FP-DP) to overcome the drawbacks of low transport of chemotherapeutics across the blood–tumor barrier and poor multidrug-resistant (MDR) tumor therapy. c(RGDyK) that can bind to the integrin protein richly expressed at the site of tumor vascular endothelial cells and tumor cells with high affinity and specificity was conjugated to the N -hydroxysuccinimide-activated PEO terminus of the Pluronic F127 block copolymer. In this study, decreased tumor angiogenic and increased apoptotic activity in MDR cancer cells were observed after the treatment with c(RGDyK)-FP-DP. c(RGDyK)-FP-DP was fully characterized in terms of morphology, particle size, zeta potential, and drug release. Importantly, in vitro antiangiogenesis results demonstrated that c(RGDyK)-FP-DP had a significant inhibition effect on the tubular formation of human umbilical vein endothelial cells and promoted cellular apoptotic activity in MDR KBv cells. In addition, the growth inhibition efficacy of KBv tumor spheroids after crossing the blood–tumor barrier was obviously increased by c(RGDyK)-FP-DP compared to other control groups. Results suggested that c(RGDyK)-decorated Pluronic polymeric micelles can take pharmacological action on both human umbilical vein endothelial cells and KBv MDR cancer cells, resulting in a dual-functional anticancer effect similar to that observed in our in vitro cellular studies.

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“…Microtubule inhibitor docetaxel, which is semi-synthetically derived from a natural compound extracted from the pacific yew tree Taxus, belongs to the most active cytotoxic drug in patients with metastatic breast cancer. However, most of breast cancer patients relapse upon or after treatment due to either intrinsic or acquired drug resistance [13]. Systemic toxicity can seriously decrease the effectiveness of the drug as well, that's why a lower dose must be administrated to avoid drug toxicity.…”

Section: Introductionmentioning

confidence: 99%

“…Although the reduction of intracellular drug level due to the P-glycoprotein pump is considered to be the main mechanism in drug resistance [12] and the expression product of the drug-metabolizing enzymes may be responsible for the resistance as well. The overexpression of trans-membrane receptor tyrosine kinase HER2 is associated with increased tumor aggressiveness and chemoresistance to several anti-cancer drugs including docetaxel and paclitaxel [13,14].…”

Section: Introductionmentioning

confidence: 99%

Enhancement of docetaxel-treated MCF-7 cell death by 900-MHz radiation

et al. 2013

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The aim of the study was to investigate the effect of high-frequency electromagnetic field of 900 MHz at 8 W input power on metabolic activity of human breast adenocarcinoma MCF-7 cells. With the aid of the colorimetric MTT assay, it was shown that there is significant change in cell culture survival exposed to docetaxel in field-free conditions in comparison with cells treated with docetaxel simultaneously exposed to high-frequency electromagnetic field.

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Taxane resistance in breast cancer: A closed HER2 circuit?

Cited by 27 publications

References 133 publications

Analysis of wntless (WLS) expression in gastric, ovarian, and breast cancers reveals a strong association with HER2 overexpression

Analysis of wntless (WLS) expression in gastric, ovarian, and breast cancers reveals a strong association with HER2 overexpression

Dual-functional c(RGDyK)-decorated Pluronic micelles designed for antiangiogenesis and the treatment of drug-resistant tumor

Enhancement of docetaxel-treated MCF-7 cell death by 900-MHz radiation

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