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Emil Lou
Division of HOT
Novel Biomarkers of Chemoresistant Ovarian Cancers
Emil Lou, Michael Linden, Matthew Gerber, Phillip Wong, RI Vogel, Minnu Monu, Jaai
Deshpande, Chap Le, Gregory Vercellotti, Subbaya Subramanian, Clifford J Steer, Deanna
Teoh, Melissa Geller
Introduction: The 5-year survival rate for ovarian cancer remains poor at 47%. Standard-ofcare treatment for ovarian cancer is platinum-based chemotherapy; however, 20-30% of
patients with ovarian cancer have platinum-resistant disease. The objective of this
prospective patient-based biomarker clinical trial is to determine whether candidate
biomarkers in tumor tissue or in blood correlate with levels of platinum chemoresistance and,
therefore, could serve as potential diagnostic and prognostic indicators of patient outcome.
Aim 1: Assess the role of ERCC1 in platinum resistance of ovarian cancer.
Aim 2: Assess the role of microRNAs 199a and 29b in platinum resistance of ovarian cancer.
Aim 3: Assess circulating tumor cells (CTCs) and intra-tumor stroma proportion as prognostic
biomarkers of recurrence and platinum sensitivity.
Methods: To date, we have enrolled 35 women with newly diagnosed advanced ovarian
tumors. We are examining and quantitating differences in miRNAs 199a and 29b, and ERCC1
in their surgically resected tumors, and CTC concentrations from their blood samples collected
at time of initial clinic visit and enrollment. Prospectively, we are following patient outcomes,
including progression-free survival (PFS) and overall survival (OS). Outcomes will be correlated
to patient status based on clinical assessment of platinum-resistance or platinum-sensitivity.
Anticipated Results: We expect that ERCC1 and miRNAs 199a and 29b are overexpressed in
platinum-resistant ovarian cancers, and that CTC concentration correlates with
chemoresistance. We expect that stroma-high tumors have worse prognosis and an increased
incidence of platinum-resistance.
Translation:
 This trial will identify novel biomarkers of platinum chemotherapy resistance.
 Our prospective study will have significant translational impact by directly
correlating these biomarkers to clinical outcomes.
 The identified novel biomarkers will then be used in future correlative studies to
more effectively tailor treatments to women suffering from this refractory
malignancy.
Conclusions: We believe that our approach will provide insight into the mechanisms of
chemotherapy resistance taking place in patients with ovarian tumors and will address a major
clinical problem in ovarian cancer treatment.