Expression of the Tumor Suppressor Gene ARHI in Epithelial Ovarian Cancer Is Associated with Increased Expression of p21WAF1/CIP1 and Prolonged Progression-Free Survival

ObjectiveTo investigate the efficacy and safety of hu3S193, a humanized anti-Lewis-Y monoclonal antibody, as a consolidation strategy in patients with platinum-sensitive recurrent epithelial ovarian cancer who achieved a second complete response after salvage platinum-doublet chemotherapy.MethodsThis single-arm phase II study accrued patients with recurrent epithelial ovarian cancer with Lewis-Y expression by immunohistochemistry who had achieved a second complete response after five to eight cycles of platinum-based chemotherapy. Patients received intravenous infusions of hu3S193, 30 mg/m2 every 2 weeks starting no more than 8 weeks after the last dose of chemotherapy and continuing for 12 doses, until disease progression, or unacceptable toxicity. The primary endpoint was progression-free survival of the second remission. Secondary objectives were safety and pharmacokinetics.ResultsTwenty-nine patients were enrolled. Most had a papillary/serous histology tumor (94%), stage III disease at diagnosis (75%), and five (17%) underwent secondary cytoreduction before salvage chemotherapy. Two patients were not eligible for efficacy but were considered for toxicity analysis. Eighteen patients (62%) completed the full consolidation treatment while nine patients progressed on treatment. At the time of analysis, 23 patients (85%) of the eligible population had progressed and seven of these patients (26%) had died. Median progression-free survival of the second remission was 12.1 months (95% CI: 10.6–13.9), with a 1-year progression-free survival of the second remission rate of 50.1%. The trial was terminated early since it was unlikely that the primary objective would be achieved. The most commonly reported treatment-related adverse events were nausea (55%) and vomiting (51%).ConclusionsHu3S193 did not show sufficient clinical activity as consolidation therapy in patients with recurrent epithelial ovarian cancer who achieved a second complete response after platinum-based chemotherapy.Trial registrationNCT01137071.

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Association of serum autoantibodies to tumor-suppressor gene p53 in patients with ovarian cancer according to status of the disease

Oncology Reports ◽

10.3892/or.4.6.1157 ◽

1997 ◽

Author(s):

D Marx ◽

T Uebel ◽

A Schauer ◽

W Kuhn ◽

H Meden

Keyword(s):

Ovarian Cancer ◽

Tumor Suppressor ◽

Tumor Suppressor Gene ◽

Suppressor Gene ◽

Tumor Suppressor Gene P53

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Correlation of PKM2 and CD44 Protein Expression with Poor Prognosis in Platinum-Treated Epithelial Ovarian Cancer: A Retrospective Study

Cancers ◽

10.3390/cancers12041013 ◽

2020 ◽

Vol 12 (4) ◽

pp. 1013

Author(s):

Chara Papadaki ◽

Stavroula Manolakou ◽

Eleni Lagoudaki ◽

Spyros Pontikakis ◽

Despo Ierodiakonou ◽

...

Keyword(s):

Ovarian Cancer ◽

Overall Survival ◽

Prognostic Factor ◽

Protein Expression ◽

Epithelial Ovarian Cancer ◽

Cancer Cells ◽

Progression Free Survival ◽

Free Survival ◽

Protein Levels ◽

Low Expression

CD44, a surface marker for cancer stem cells, interacts with PKM2, a key regulator of aerobic glycolysis, and enhances the glycolytic phenotype of cancer cells leading to antioxidant protection and macromolecules’ synthesis. To clarify the clinical importance of this “cross-talk” as a mechanism of drug resistance, we assessed the expression both of PKM2 and of CD44 in cancer cells of patients with epithelial ovarian cancer (EOC) treated with platinum-based treatment. One hundred and seventy-one patients with EOC were assessed for PKM2mRNA expression and PKM2 and CD44 proteins detection. Associations with progression-free survival (PFS) and overall survival (OS) were assessed with Kaplan–Meier and adjusted Cox regression models. PKM2mRNA and protein as well as CD44 protein were detectable in the majority of patients. Positive correlation between PKM2 and CD44 protein expression was observed (Spearman rho = 0.2, p = 0.015). When we used the median to group patients into high versus low expression, high PKM2mRNA and protein levels were significantly associated with lower progression-free survival (PFS; p = 0.003 and p = 0.002, respectively) and shorter overall survival (OS; p ≤ 0.001 and p = 0.001, respectively). However, high CD44 protein expression was significantly correlated only with shorter OS (p = 0.004). Moreover, patients with both high PKM2 and CD44 protein levels experienced shorter PFS and OS (p = 0.007 and p = 0.003, respectively) compared to patients with low expression of both proteins. Finally, higher PKM2mRNA and protein expression as well as CD44 protein expression (HR: 2.16; HR: 1.82; HR: 1.01, respectively) were independent prognostic factors for decreased median OS (mOS), whereas only PKM2 protein expression (HR: 1.95) was an independent prognostic factor for decreased median PFS (mPFS). In conclusion, PKM2 expression is a negative prognostic factor in EOC patients, but the interaction between CD44 and PKM2 that may be implicated in EOC platinum-resistance needs further investigation.

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