Lewis(y) antigen promotes the progression of epithelial ovarian cancer by stimulating MUC1 expression

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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Serological and immunochemical analysis of Lewis Y (Ley) blood group antigen expression in epithelial ovarian cancer

International Journal of Cancer ◽

10.1002/(sici)1097-0215(19960208)65:4<406::aid-ijc2>3.0.co;2-0 ◽

1996 ◽

Vol 65 (4) ◽

pp. 406-412 ◽

Cited By ~ 59

Author(s):

Beatrice W. T. Yin ◽

Connie L. Finstad ◽

Kunio Kitamura ◽

Mark G. Federici ◽

Marie Welshinger ◽

...

Keyword(s):

Ovarian Cancer ◽

Epithelial Ovarian Cancer ◽

Blood Group ◽

Antigen Expression ◽

Blood Group Antigen ◽

Immunochemical Analysis ◽

Lewis Y

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Expression of CD147 and Lewis y antigen in ovarian cancer and their relationship to drug resistance

Medical Oncology ◽

10.1007/s12032-014-0920-9 ◽

2014 ◽

Vol 31 (5) ◽

Cited By ~ 18

Author(s):

Jian Gao ◽

Zhenhua Hu ◽

Juanjuan Liu ◽

Dawo Liu ◽

Yanyan Wang ◽

...

Keyword(s):

Ovarian Cancer ◽

Drug Resistance ◽

Lewis Y Antigen ◽

Lewis Y

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Overexpression of Lewis (y) Antigen Protects Ovarian Cancer RMG-1 Cells from Carboplatin-Induced Apoptosis by the Upregulation of Topo-I and Topo-II β

The Anatomical Record ◽

10.1002/ar.21398 ◽

2011 ◽

Vol 294 (6) ◽

pp. 961-969 ◽

Cited By ~ 9

Author(s):

Changzhi Wang ◽

Limei Yan ◽

Yifei Wang ◽

Bei Lin ◽

Shuice Liu ◽

...

Keyword(s):

Ovarian Cancer ◽

Lewis Y Antigen ◽

Lewis Y ◽

Topo Ii ◽

Induced Apoptosis

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Human Epididymis Protein 4 and Lewis y Enhance Chemotherapeutic Resistance in Epithelial Ovarian Cancer Through the p38 MAPK Pathway

Advances in Therapy ◽

10.1007/s12325-021-01941-1 ◽

2021 ◽

Author(s):

Jian Gao ◽

Liancheng Zhu ◽

Huiyu Zhuang ◽

Bei Lin

Keyword(s):

Ovarian Cancer ◽

Epithelial Ovarian Cancer ◽

P38 Mapk ◽

Mapk Pathway ◽

Chemotherapeutic Resistance ◽

Human Epididymis Protein 4 ◽

Human Epididymis ◽

P38 Mapk Pathway ◽

Lewis Y

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Human epididymis protein 4 and Lewis y enhance chemotherapeutic resistance in epithelial ovarian cancer through the p38MAPK pathway

10.21203/rs.3.rs-149925/v1 ◽

2021 ◽

Author(s):

Jian Gao ◽

Liancheng Zhu ◽

Huiyu Zhuang ◽

Song Gao ◽

Bei Lin

Keyword(s):

Ovarian Cancer ◽

Cancer Patients ◽

Mapk Pathway ◽

Chemotherapy Resistance ◽

Gene Signature ◽

Biological Behavior ◽

Ovarian Cancer Cell Lines ◽

Lewis Y Antigen ◽

Lewis Y ◽

Cancer Tissues

Abstract Background Ovarian cancer has a high mortality rate due to difficulties in early detection and chemotherapy resistance. Human epididymal protein 4 (HE4) has been adopted as a novel serum biomarker for early ovarian cancer diagnosis, we have previously detected the presence of Lewis y antigen modifications on HE4 in ovarian cancer cell lines. In this study, we aimed to analyze the expression of HE4 and Lewis y antigen in human ovarian cancer in order to analyze their correlation with each other, as well as with the clinical pathological parameters of ovarian cancer patients. Methods We first used immunohistochemistry to detect the respective expressions of these compounds in two patient groups (chemotherapy-resistant and -sensitive) containing a total of 95 patients. Then, we adopted a bioinformatic approach and used online large-sample databases (TCGA, CCLE and GTEx; Metascape, Cytoscape) to explore the potential mechanisms of action of these compounds. Results Our results demonstrate that high HE4 and Lewis y expressions could be used as markers for chemotherapy-resistance and poor prognosis in ovarian cancer patients. These two expressions were widely correlated in various cancer tissues and are thought to act by activating the p38 MAPK pathway and inducing VEGFA, PTGS2,EGR1,andHIFI1A, thereby promoting malignant biological behavior and resistance in ovarian cancer. Conclusions This finding not only reveals the possible mechanism by which HE4 and Lewis y antigen affect ovarian cancer, but also identifies a four-gene signature that could be very useful in ovarian cancer detection and/or the development of new targeted therapies.

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