The establishment, characterization and calibration of human ovarian carcinoma xenografts for the evaluation of novel platinum anticancer drugs.
Twenty-three serially transplantable ovarian carcinoma xenografts have been established in female nude mice from forty-two donor samples provided by both previously treated and untreated patients. The lines are all of human karyotype and mirror the histopathology of the original explant. Sixteen examples have been calibrated against four reference platinum drugs: cisplatin, carboplatin, iproplatin, tetraplatin. Three distinct patterns of response were observed: (i) tumours which were comparably sensitive to all four drugs (2 lines); (ii) tumours which were comparably refractory to treatment with all four drugs (5 lines); (iii) tumours which exhibited "individual" patterns of response to the group of calibrating drugs (9 lines). The "response rate" overall of the tumour panel to each of the clinically used drugs was 44% (7/16), though the pattern of response was not identical for each drug. Only 2/16 tumours (13%) were sensitive to tetraplatin, these also being the same tumours which were particularly sensitive to the other three drugs. It was also possible to confirm in 8/9 lines that the therapeutic response of the xenograft reflected that of the corresponding patient's tumour to platinum-based chemotherapy. This tumour panel has now been adopted for evaluating novel platinum-based drugs designed specifically for the treatment of ovarian cancer.
Harrap
K R
KR
Drug Development Section, Institute of Cancer Research, Belmont, Sutton, Surrey, UK.
Jones
M
M
Siracky
J
J
Pollard
L A
LA
Kelland
L R
LR
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D016190:Carboplatin / Q000494:pharmacology; D002460:Cell Line; D002945:Cisplatin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009944:Organoplatinum Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D014183:Transplantation, Heterologous
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; C023359:iproplatin; D016190:Carboplatin; D002945:Cisplatin; C049777:ormaplatin