Article Text
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.