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Friday May 24, 2024 from 17:45 to 20:00

Room: Regency

> Poster POS-63 Microfluidics based culture and treatment of micro-dissected tissues, a novel ex vivo models to predict clinical response to carboplatin-paclitaxel chemotherapy in high-grade serous ovarian cancer patients

Isaline Bontemps

Post-doctoral fellow
CRCHUM

Abstract

Microfluidics based culture and treatment of micro-dissected tissues, a novel ex vivo models to predict clinical response to carboplatin-paclitaxel chemotherapy in high-grade serous ovarian cancer patients

Isaline BONTEMPS1,4, Benjamin PEANT1, Sabrina RITCH1, Jennifer KENDALL-DUPONT1, Dina DORRIGIV1,2, Kayla SIMEONE1, Thomas GERVAIS1,2, Diane PROVENCHER1,3, Anne-Marie MES-MASSON1,4.

1Institut du cancer de Montréal/Centre de recherche du Centre hospitalier de l’Université de Montréal, Montréal, QC, Canada; 2Polytechnique de Montréal, Montréal, QC, Canada; 3Division de gynécologie oncologique, Université de Montréal, Montréal, QC, Canada; 4Département de médecine, Université de Montréal, Montréal, QC, Canada

Introduction: High-grade serous ovarian carcinoma is initially a largely asymptomatic disease and thus frequently diagnosed at an advanced stage. Current treatment for this often-lethal gynecological cancer is a combination chemotherapy based on carboplatin and paclitaxel either before or after extensive resection surgery. While initial response to chemotherapy is high, approximately 20% of patients will demonstrate innate resistance to the chemotherapeutic regimen causing severe side effects without appreciable clinical benefit. Therefore, a main challenge in ovarian cancer research remains to identify patients with resistant or refractory disease before starting treatment.

Methods: To predict treatment response and adapt therapeutic strategies for each patient, we have developed a new ex-vivo tumor-derived model as a tool for personalized medicine. In brief, micro-dissected tissues (MDTs) are generated from patient’s ovarian tumors, then cultured and treated within microfluidic devices. The proportion of epithelial cells within the MDTs is monitored. Response to drug is monitored via Ki67 expression for proliferation cells and cleaved caspase-3 to assess apoptosis.

Results: By comparing response biomarker expression in treated and non-treated MDTs, we classified ex vivo tumor response as either resistant or sensitive. The designation is subsequently compared to the observed patient clinical response as determined up to 6 months after the end of treatment. In 13 patients, while results with cleaved caspase 3 are inconsistent, we observed high expression of Ki67 and the proportion of epithelium after drug treatment only in MDT from resistant/refractory patients. We are presently extending the analysis to optimize discrimination thresholds for biomarkers and achieve statistical significance.

Conclusion: Our study provides initial promising results for the use of microfluidics-based ex vivo testing as a predictive tool for treatment response of ovarian cancer patient.

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