Predictive markers of chemoresistance in advanced stages epithelial ovarian carcinoma

Bonneau, Claire; Rouzier, Roman; Geyl, Caroline; Cortez, Annie; Castela, Mathieu; Lis, Raphaël; Daraı̈, Émile; Touboul, Cyril

doi:10.1016/j.ygyno.2014.10.024

Cited by 42 publications

(33 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We detected increased CD44 expression in treated regrowing xenografts, corroborating its recently reported higher expression in recurrent and metastatic ovarian samples than their primary counterparts [48]. However, even CD44+ cell enrichment has been reported in the majority of ovarian cancer samples after neoadjuvant therapy, no significant association with chemoresistance was reported and a decrease in CD44 expression was associated with shorter survival [49]. …”

Section: Discussionsupporting

confidence: 86%

Patient-derived ovarian cancer xenografts re-growing after a cisplatinum treatment are less responsive to a second drug re-challenge: a new experimental setting to study response to therapy

et al. 2016

View full text Add to dashboard Cite

Even if ovarian cancer patients are very responsive to a cisplatinum-based therapy, most will relapse with a resistant disease. New experimental animal models are needed to explore the mechanisms of resistance, to better tailor treatment and improve patient prognosis. To address these aims, seven patient-derived high-grade serous/endometrioid ovarian cancer xenografts were characterized for the antitumor response after one and two cycles of cisplatinum and classified as Very Responsive, Responsive, and Low Responsive to drug treatment. Xenografts re-growing after the first drug cycle were much less responsive to the second one. The expression of epithelial-mesenchymal transition (EMT) and cancer stem cells (CSCs) genes was investigated in cisplatinum-treated and not-treated tumors. We found that different EMT (TCF3, CAMK2N1, EGFR, and IGFBP4) and CSCs (SMO, DLL1, STAT3, and ITGA6) genes were expressed at higher levels in Low Responsive than in Responsive and Very Responsive xenografts. The expression of STAT3 was found to be associated with lower survival (HR = 13.7; p = 0.013) in the TCGA patient data set. MMP9, CD44, DLL4, FOXP1, MERTK, and PTPRC genes were found more expressed in tumors re-growing after cisplatinum treatment than in untreated tumors. We here describe a new in vivo ovarian carcinoma experimental setting that will be instrumental for specific trials of combination therapy to counteract cisplatinum resistance in order to improve the prognosis of ovarian patients.

show abstract

Section: Discussionsupporting

confidence: 86%

Patient-derived ovarian cancer xenografts re-growing after a cisplatinum treatment are less responsive to a second drug re-challenge: a new experimental setting to study response to therapy

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Through comparison of chemoresistant and chemosensitive primary OC tissue samples, Bonneau et al found that CD44 expression on tumor cells appeared to correlate with OS and could be used as a predictor of chemoresistance [79]. Similarly, by comparing the paired primary, metastatic, recurrent OC tissues from 26 individual patients, another study showed that both the metastatic and recurrent tissues expressed higher level of CD44 than the patient matched primary tumors, and a significant association was found between CD44 expression and both the DFS and OS.…”

Section: Cscs In Ovarian Cancer Chemoresistancementioning

confidence: 99%

Targeting epithelial-mesenchymal transition and cancer stem cells for chemoresistant ovarian cancer

et al. 2016

View full text Add to dashboard Cite

Chemoresistance is the main challenge for the recurrent ovarian cancer therapy and responsible for treatment failure and unfavorable clinical outcome. Understanding mechanisms of chemoresistance in ovarian cancer would help to predict disease progression, develop new therapies and personalize systemic therapy. In the last decade, accumulating evidence demonstrates that epithelial-mesenchymal transition and cancer stem cells play important roles in ovarian cancer chemoresistance and metastasis. Treatment of epithelial-mesenchymal transition and cancer stem cells holds promise for improving current ovarian cancer therapies and prolonging the survival of recurrent ovarian cancer patients in the future. In this review, we focus on the role of epithelial-mesenchymal transition and cancer stem cells in ovarian cancer chemoresistance and explore the therapeutic implications for developing epithelial-mesenchymal transition and cancer stem cells associated therapies for future ovarian cancer treatment.

show abstract

“…The sample sizes of the included studies ranged from 11 to 440. Among these studies, 15 studies involved patients with ALDH1 [19, 22, 26, 30-41], 8 studies involved patients with CD133 [18, 23, 25, 30, 31, 37, 42, 43], 25 studies involved patients with CD44 [17, 21, 24, 44-64, 66], 7 studies involved patients with CD117 [13, 20, 26, 27, 67-69], 3 studies involved patients with ALDH1 and CD133 [30, 31, 37], and 1 study involved patients with ALDH1 and CD117 [26]. According to the NOS quality assessment, 52 of the studies were categorized as high quality.…”

Section: Resultsmentioning

confidence: 99%

Clinicopathological and Prognostic Significance of Cancer Stem Cell Markers in Ovarian Cancer Patients: Evidence from 52 Studies

Tao

Huang

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: Relevant markers of cancer stem cells (CSCs) may serve as commonly used biomarkers of ovarian cancer (OC). However, their actual clinicopathological and prognostic significance remains inconclusive. Thus, we conducted a meta-analysis to quantitatively evaluate the association between the expression of CSC-relevant markers (ALDH1, CD117, CD133, and CD44) and OC. Methods: We used an odds ratio (OR) and a hazard ratio (HR) with a 95% confidence interval (CI) to estimate the effects by analyzing 52 studies from a literature search. Heterogeneity and sensitivity were evaluated, as well. Publication bias was assessed using funnel plots and Egger tests. Results: ALDH1 expression was statistically associated with FIGO stage (OR=1.872, 95%CI=1.14-3.076, P=0.013) and lymph invasion (OR=2.78, 95%CI=1.08-7.152, P=0.034). CD117 expression was significantly associated with FIGO stage (OR=2.01, 95%CI=1.35-2.98, P=0.001). CD133 expression was correlated with FIGO stage (OR=3.410, 95%CI=2.196-5.294, P< 0.001) and differentiation grade (OR=2.672, 95%CI=1.354-5.272, P=0.005). CD44s was related to chemotherapy resistance (OR=3.218, 95%CI=1.148-9.016, P=0.026). Furthermore, overexpression of ALDH1 (HR=1.494, 95%CI=1.207-1.849, P< 0.001), CD117 (HR=1.395, 95%CI=1.025-1.898, P=0.034) or CD44s (HR=1.725, 95%CI=1.135-2.623, P=0.011) was associated with poor OS. Further, overexpression of both ALDH1 (HR=1.524, 95%CI=1.158-2.007, P=0.003) and CD44s (HR=2.12, 95%CI=1.692-2.657, P< 0.001) was correlated with worse DFS. Conclusion: CSC markers are useful predictive or prognostic biomarkers for OC in clinical assessments. Combined detection of CSC marker expression may be a powerful tool for prognostic predictions in clinical practice for patients with OC.

show abstract

Predictive markers of chemoresistance in advanced stages epithelial ovarian carcinoma

Cited by 42 publications

References 35 publications

Patient-derived ovarian cancer xenografts re-growing after a cisplatinum treatment are less responsive to a second drug re-challenge: a new experimental setting to study response to therapy

Patient-derived ovarian cancer xenografts re-growing after a cisplatinum treatment are less responsive to a second drug re-challenge: a new experimental setting to study response to therapy

Targeting epithelial-mesenchymal transition and cancer stem cells for chemoresistant ovarian cancer

Clinicopathological and Prognostic Significance of Cancer Stem Cell Markers in Ovarian Cancer Patients: Evidence from 52 Studies

Contact Info

Product

Resources

About