The Culture of Advanced or Recurrent Ovarian Cancer Organoids and Drug Screening

Most ovarian cancer will relapse after standard therapy. Patients with recurrent ovarian cancer are resistant to platinum. Due to the high heterogeneity between ovarian cancer, individual precise therapy is of great importance. The study will establish ovarian cancer organoids, whose original tissues from the patients with advanced or recurrent ovarian cancer, their tumors cannot be excised completely. The organoids will be identified at the histopathological level and gene level for evaluating the consistency with the original tumor tissue. The drug's sensitivity and specificity are detected through the organoids model. Compared with the clinical efficiency of the actual drug regimen, the efficacy of the organoid drug screening model can be assessed. The aim is to construct a precise drug screening platform for advanced and recurrent ovarian cancer patients and innovate drug research and development.

Sex

Female

Minimum age

18 Years

Maximum age

70 Years

Inclusion Criteria:

1. Patients voluntarily participated in the study and signed informed consent;
2. The tumour cannot be excised thoroughly by surgery;
3. ECOG score ≤ 2;
4. Expected survival \>6 months;
5. Blood routine test: Hb≥70g/L、WBC≥3.5×109/ L 、ANC≥1.5×109/L、PLT≥80×109/L;
6. Both serum ALT and serum AST ≤ 2 × ULN； blood creatinine ≤ 1.5 × ULN;
7. Unpregnant women (negative HCG) received contraception in the study;
8. Good compliance is judged by researchers.

Exclusion Criteria:

1. Active or the uncontrol serious infections;
2. Patients with liver cirrhosis, decompensated liver disease, active hepatitis or chronic hepatitis need antiviral treatment;
3. A history of immune deficiency, including HIV positive or other acquired congenital immune deficiency diseases;
4. Chronic renal insufficiency and renal failure;
5. Myocardial infarction, severe arrhythmia and congestive heart failure (≥ grade 2 according to NYHA classification);
6. Autoimmune diseases, including systemic lupus erythematosus;
7. Patients take drugs that damage liver and kidney function for other complications, such as tuberculosis;
8. Patients cannot understand the experimental contents and refuse to sign the informed consent form;
9. Other concomitant serious diseases harm the health of patients or interfere with the study.

• BACKGROUNDTuveson D, Clevers H. Cancer modeling meets human organoid technology. Science. 2019 Jun 7;364(6444):952-955. doi: 10.1126/science.aaw6985. PMID 31171691
• BACKGROUNDSachs N, Clevers H. Organoid cultures for the analysis of cancer phenotypes. Curr Opin Genet Dev. 2014 Feb;24:68-73. doi: 10.1016/j.gde.2013.11.012. Epub 2013 Dec 31. PMID 24657539
• BACKGROUNDChen Z, Fillmore CM, Hammerman PS, Kim CF, Wong KK. Non-small-cell lung cancers: a heterogeneous set of diseases. Nat Rev Cancer. 2014 Aug;14(8):535-46. doi: 10.1038/nrc3775. PMID 25056707
• BACKGROUNDBertotti A, Migliardi G, Galimi F, Sassi F, Torti D, Isella C, Cora D, Di Nicolantonio F, Buscarino M, Petti C, Ribero D, Russolillo N, Muratore A, Massucco P, Pisacane A, Molinaro L, Valtorta E, Sartore-Bianchi A, Risio M, Capussotti L, Gambacorta M, Siena S, Medico E, Sapino A, Marsoni S, Comoglio PM, Bardelli A, Trusolino L. A molecularly annotated platform of patient-derived xenografts ("xenopatients") identifies HER2 as an effective therapeutic target in cetuximab-resistant colorectal cancer. Cancer Discov. 2011 Nov;1(6):508-23. doi: 10.1158/2159-8290.CD-11-0109. Epub 2011 Sep 2. PMID 22586653
• BACKGROUNDZhao X, Liu Z, Yu L, Zhang Y, Baxter P, Voicu H, Gurusiddappa S, Luan J, Su JM, Leung HC, Li XN. Global gene expression profiling confirms the molecular fidelity of primary tumor-based orthotopic xenograft mouse models of medulloblastoma. Neuro Oncol. 2012 May;14(5):574-83. doi: 10.1093/neuonc/nos061. Epub 2012 Mar 29. PMID 22459127
• BACKGROUNDBergamaschi A, Hjortland GO, Triulzi T, Sorlie T, Johnsen H, Ree AH, Russnes HG, Tronnes S, Maelandsmo GM, Fodstad O, Borresen-Dale AL, Engebraaten O. Molecular profiling and characterization of luminal-like and basal-like in vivo breast cancer xenograft models. Mol Oncol. 2009 Dec;3(5-6):469-82. doi: 10.1016/j.molonc.2009.07.003. Epub 2009 Aug 4. PMID 19713161