Predicting response to the anti-estrogen fulvestrant in recurrent ovarian cancer

Argenta, Peter A.; Um, Inhwa; Kay, Charlene; Harrison, David J.; Faratian, Dana; Sueblinvong, Thanasak; Geller, Melissa A.; Langdon, Simon P.

doi:10.1016/j.ygyno.2013.07.099

Cited by 22 publications

(29 citation statements)

References 30 publications

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“…ERα expression was correlated with clinical benefit in this study and TFF1 and vimentin expression were both predictive of progression-free survival (178).…”

Section: A C C E P T E D Accepted Manuscriptsupporting

confidence: 55%

Treating gynecologic malignancies with selective estrogen receptor downregulators (SERDs): promise and challenges

Boisen

Andersen

Sreekumar

et al. 2015

Molecular and Cellular Endocrinology

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“…ERα expression was correlated with clinical benefit in this study and TFF1 and vimentin expression were both predictive of progression-free survival (178).…”

Section: A C C E P T E D Accepted Manuscriptsupporting

confidence: 55%

Treating gynecologic malignancies with selective estrogen receptor downregulators (SERDs): promise and challenges

Boisen

Andersen

Sreekumar

et al. 2015

Molecular and Cellular Endocrinology

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“…Several of these markers (HER2, TFF1, IGFBP5 and VIM) were validated in the 2 nd Letrozole study [63]. Two of these biomarkers (TFF1 and VIM) correlated with an improved progression-free survival from material obtained in the fulvestrant study [71]. These studies now require further validation to confirm the possible value of these biomarkers.…”

Section: Predictive Biomarkersmentioning

confidence: 94%

“…A more recent study [71] has analysed fixed tissue from the ovarian cancers treated in the Phase II fulvestrant trial [61]. Within this trial, approximately half of the 26 patients treated derived clinical benefit at 90 days as assessed by either modified Rustin CA125 criteria (43%) or RECIST criteria (50%) [61].…”

Section: Predictive Biomarkersmentioning

confidence: 99%

“…Clinical benefit (CB) was assessed as the sum of complete and partial responses and disease stabilisation as opposed to progressive disease [61]. The clinical benefit group had a statistically higher mean ER immunoscore than the progressive disease group consistent with a higher level of ER expression being associated with improved outcome [71].…”

Section: Predictive Biomarkersmentioning

confidence: 99%

“…While ER expression was evaluated in most of the AI trials, it was generally to confirm that a minimum level of expression was present hence expression of > 1% cells positive as indicated by immunohistochemistry was regarded as indicative of ERpositivity. The studies using more detailed immunoscoring suggest that higher levels of ER expression than the minimum are more likely to be associated with response [17,63,71]. The study by Papadimitriou [62] did evaluate high, intermediate low and negative levels of ER but could not find an association with response, however the investigators did note that the 3 responders were all ER-positive [62].…”

Section: Predictive Biomarkersmentioning

confidence: 99%

See 2 more Smart Citations

Endocrine therapy in epithelial ovarian cancer

Langdon

Gourley

Gabra

et al. 2016

Expert Review of Anticancer Therapy

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Introduction:The estrogen receptor (ER) is expressed at high levels in many epithelial ovarian cancers (EOC) and represents a potential target for endocrine therapy. Both anti-estrogens and aromatase inhibitors have been evaluated in phase II clinical trials. Areas covered:We present an overview of the phase II and phase III trials of anti-estrogens (tamoxifen and fulvestrant) and aromatase inhibitors (letrozole, anastrazole and exemestane) undertaken in epithelial ovarian cancer identified through a Pubmed search. We describe predictive biomarkers that are being investigated to identify responsive cancers. Expert commentary:The efficacy of endocrine therapy in epithelial ovarian cancer is likely to be confined to histological subtypes with the highest ER expression while low grade serous ovarian cancer appears to be one subgroup with good sensitivity to these agents. The low toxicity profile of these agents is favourable although their use is unlicensed and the optimal setting undefined. Prospective clinical trials of endocrine agents in the early relapse and maintenance settings are urgently required to establish their definitive role in the management of epithelial ovarian cancer

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Epithelial‐to‐Mesenchymal Transition in Paclitaxel‐Resistant Ovarian Cancer Cells Is Downregulated by Luteolin

Dia

Pangloli

2016

Journal Cellular Physiology

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Ovarian cancer (OVCA) is the deadliest of all gynecological cancers which is attributed to late presentation, persistence, and development of chemoresistance. The objectives were to evaluate the association between OVCA paclitaxel-resistance and epithelial-to-mesenchymal transition (EMT) and to determine the capability of luteolin to chemosensitize OVCA cells. X10 and X22 cells were 11.8-25.3-fold and 7.8-8.6-fold resistant to paclitaxel than 1AP cells. X10 and X22 cells exhibited a mesenchymal phenotype, while 1AP has an epithelial characteristics. Furthermore, the expression of the epithelial marker E-cadherin was downregulated, while mesenchymal markers Vimentin and N-cadherin were upregulated in X10 and X22 cells when compared to 1AP cells. Transcription factors Snail, Slug, and Twist1 were upregulated in X10 cells, while Twist1 was highly expressed in X22 cells. Luteolin treatment caused cytotoxicity being most potent to X10 OVCA cells. Treatment of non-cytotoxic dose of luteolin at 15.625 μM chemosensitized X10 and X22 OVCA cells to paclitaxel as evidenced by reduced ED values from 11.8 to 0.2 μM and 8.6 to 3.6 μM for X10 and X22 cells, respectively. Moreover, luteolin treatment led to a more epithelial phenotype of X10 and X22 cells and modification of EMT markers indicating reversal of EMT. The mechanism involved is through reduction of phosphorylation of FAK and ERK leading to reduced nuclear translocation of p65. Our results highlight the significance of EMT in OVCA resistance to paclitaxel and warrant the investigation of luteolin as a potential therapeutic agent in chemoresistant OVCA. J. Cell. Physiol. 232: 391-401, 2017. © 2016 Wiley Periodicals, Inc.

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Predicting response to the anti-estrogen fulvestrant in recurrent ovarian cancer

Cited by 22 publications

References 30 publications

Treating gynecologic malignancies with selective estrogen receptor downregulators (SERDs): promise and challenges

Treating gynecologic malignancies with selective estrogen receptor downregulators (SERDs): promise and challenges

Endocrine therapy in epithelial ovarian cancer

Epithelial‐to‐Mesenchymal Transition in Paclitaxel‐Resistant Ovarian Cancer Cells Is Downregulated by Luteolin

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