Trial Information

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

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.