Characterization of Ovarian Cancer Stem Cell

Ovarian Cancer Clinical Trial

Official title:

Characterization of Ovarian Cancer Stem Cell: Focus on Identification of Biomarker and Drug Resistance

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01367353
• Other study ID #: 200902010R
• Status: Recruiting
• Phase: N/A
• First received: December 10, 2010
• Last updated: June 6, 2011
• Start date: January 2010
• Est. completion date: December 2013

Study information

• Verified date: May 2011
• Source: National Taiwan University Hospital
• Contact: Wen-Fang Cheng, Professor
• Phone: 886-2-23123456
• Email: wenfangcheng[@]yahoo.com
• Is FDA regulated: No
• Health authority: Taiwan: Department of Health
• Study type: Interventional

Clinical Trial Summary

Specific aims: Identification and characterization of cancer stem cell-like population (cancer stem cells or cancer initiating cells) from primary tumor tissue, primary ascites and peripheral blood of ovarian cancer patients and genetically engineered mouse ovarian cancer cell lines.

Objectives: In the future, individualized therapy must incorporate analysis of the cancer stem cells or cancer initiating cells of ovarian cancer cells when designing therapeutic strategies for ovarian cancer patients.

Aims of this project:

1. Isolation and identification of cancer stem cell-like population (cancer stem cells or cancer initiating cells) from primary tumor tissue, primary ascites and peripheral blood of ovarian cancer patients

2. In vivo tumorigenicity assay will be performed to measure tumor formation from these cancer stem cell-like population when equal numbers were injected into the dorsal fat pad of nude mice.

3. To establish a standard protocol of stem cell-like population maintenance

4. Screening of potential specific biomarkers involved in these ovarian cancer stem cell-like population.

Description:

Ovarian cancer has the highest mortality of all gynecological cancers, with an overall 5-year survival rate of only 30-40%. The incidence of ovarian cancer also increased in recent year in Taiwan, and it became a more and more important issue. The lack of symptoms, difficulties in early diagnosis, insufficient accurate tumor markers, and lack of information about ovarian tumor biology contribute to the poor prognosis in ovarian cancer patients. The prognostic factors for ovarian carcinomas include tumor stage, subtype of histology, grade of differentiation, the residual tumor after debulking surgery, and the response to chemotherapy. Especially the resistance to chemotherapy plays a great role in the prognosis of the patients. However, the current studies present an incomplete picture of the tumor biology of ovarian cancer. It will be quite helpful to clinical management if the investigators can examine the possible underlying mechanism of tumorigenesis and drug resistance.

Malignancy usually origins from the abnormal proliferate cells which accumulate several genetic or epigenetic aberrations. The most important key question is "What kind of cell could be the cancer cell?" Recent studies figure out there is "cancer-initiating cell" in the malignant tumor. Cancer-initiating cells organized self-renewing, anchorage-independent spheres and were reproducibly. Moreover, cancer-initiating cells were also capable of intraperitoneal tumorigenesis (demonstrating activity in their native microenvironment) and could serially propagate tumors in animals. Although the proportion of the cancer-initiating cells in the cancer tissue is very low, the characteristic abilities of cancer-initiating cells fulfill all currently accepted criteria for the existence of a subpopulation of tumor-initiating cells, and their specific detection and targeting could be highly valuable for therapy of tumor heterogeneity, uncontrolled proliferation, local invasion, distant metastasis and even resistance to current management including chemotherapy.

Some tumor initiating cells which have the properties of cancer stem cells have been isolated from leukemia, breast cancer, and brain tumor. Some potential cell markers for cancer initiating cells were identified, including CD34(+)/CD38(+) in leukemia, CD44(+)/CD24(+) in breast cancer, and CD133(+)/nestin(+) in brain tumor. Aberrant cell signal transduction pathway of stem cell is associated with malignant transformation, such as Wnt, Hedgehog, and Notch pathways. Up to our knowledge, the specific antigens expressed on ovarian cancer-initiating cells have not been identified and characterized yet. In the current study, using primary human ovarian tumors, the investigators will isolate and characterized ovarian cancer-initiating cells fully capable of reestablishing their original tumor hierarchy in vivo. The investigators will also elucidate the novel diagnostic and prognostic biomarkers on ovarian cancer-initiating cells by identifying numerous differentially potential surface antigens and/or over-expressed genes. Furthermore, a mouse ovarian cancer study model will be genetically engineered and investigated to monitor the possible therapeutic effects of immunotherapy and chemotherapy to these ovarian cancer-initiating cells. The investigators hope to specify and to stratify the molecular patterns, response to chemotherapy, prognostic biomarkers in patients with ovarian cancer-initiating cells. These results might offer some novel ovarian cancer therapy hypothesis to evaluate its function on tumorigenesis and potential on targeting ovarian cancer-initiating cells.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 250
• Est. completion date: December 2013
• Est. primary completion date: December 2011
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 15 Years to 80 Years

Eligibility

Inclusion Criteria:

• Patients with ovarian carcinoma who undergo hysterectomy, bilateral oophorectomy and tubal resection, omentectomy, and appendectomy will be enrolled and the clinical data will be obtained from our hospital.

Study Design

Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Ovarian Cancer
• Ovarian Neoplasms

Intervention

Procedure:
• surgery or debulking surgery
surgery or debulking surgery

Locations

Country	Name	City	State
Taiwan	National Taiwan University Hospital	Taipei

Sponsors (1)

Lead Sponsor	Collaborator
National Taiwan University Hospital

Country where clinical trial is conducted

Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	overall survival		From disease diagnosis to death (Generally 2~5 years)	No