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PR030/#1014  Origanoid models for predicting drug response in high grade serous ovarian cancer
  1. Yangjun Wu,
  2. Zheng Feng,
  3. Ha Xinyu,
  4. Xingzhu Ju,
  5. Hao Wen and
  6. Xiaohua Wu
  1. Fudan University Shanghai Cancer Center, Department of Gynecologic Oncology, Shanghai, China

Abstract

Introduction Utilizing patient-derived organoids (PDOs) as pragmatic way to assess the effectiveness of new drugs and to identify most efficacious treatment regimens for individual patinets.

Methods Establishment of patient-derived organoid models: obtain tumor tissue from several sites (ovary, omentum, diaphragm,ect) or ascites from surgery of ovarian cancer patients in shanghai cancer center. Drug screening for organoids: Grown organoids were dissociated and re-seeded on the 384-well plated; 23 drug treatment regimens were selected including carboplatin,oxaliplatin,doxorubicin hydrochloride, olaparib, niraparib, fluzoparib, gemcitabine hydrochloride, topotecan, paclitaxel, docetaxel, Adriamycin liposome, Etoposide, Wee1 inhibitor (adavosertib), CDK4/6 inhibitor(palbociclib ), BYL-719(PI3Kα inhibitor), 5-Fluorouracil, Irinotecan, Cyclophosphamide hydrate, Vorinostat (HDACi), Ruxolitinib(JAK1/2 inhibitor), Mirvetuximab, Pemrametostat (PRMT5 inhibitor). Clinical characteristic data: clinical response was also measured by histopathological (chemotherapy response score [CRS]), biochemical (normalization of the serum biomarker CA-125), and radiological (RECIST) responses. Mechanism of platinum resistance: long-read transcriptomes for accurate identification of known and novel isoforms.

Results These PDO drug responses showed a statistically significant correlation (p < 0.05) with clinical response, as measured by CRS, CA-125, and RECIST in OV neoadjuvant patients. The capability of PDOs derived from 10 patients, including 3 platinum- sensitive, 8 PARPi-resistant recurrent OV patients to discriminate between clinically sensitive or resistant patients was determined using dose-effect curve analysis (carboplatin, olaparib, niraparib). The concordances of response were 100% (3 of 3), 75% (3 of 4) and 100% (4 of 4), respectively.

Conclusion/Implications Clinical applications of PDOs for personalized monitoring of tumor reoccurrence and in vitro drug sensitivity profiling. Palbociclib may be a better treatment option for PARPi-resistant recurrent patients.

Abstract PR030/#1014 Figure 1
Abstract PR030/#1014 Figure 2

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