Ex vivo modelling of drug efficacy in a rare metastatic urachal carcinoma

BMC Cancer. 2020 Jun 23;20(1):590. doi: 10.1186/s12885-020-07092-w.


Background: Ex vivo drug screening refers to the out-of-body assessment of drug efficacy in patient derived vital tumor cells. The purpose of these methods is to enable functional testing of patient specific efficacy of anti-cancer therapeutics and personalized treatment strategies. Such approaches could prove powerful especially in context of rare cancers for which demonstration of novel therapies is difficult due to the low numbers of patients. Here, we report comparison of different ex vivo drug screening methods in a metastatic urachal adenocarcinoma, a rare and aggressive non-urothelial bladder malignancy that arises from the remnant embryologic urachus in adults.

Methods: To compare the feasibility and results obtained with alternative ex vivo drug screening techniques, we used three different approaches; enzymatic cell viability assay of 2D cell cultures and image-based cytometry of 2D and 3D cell cultures in parallel. Vital tumor cells isolated from a biopsy obtained in context of a surgical debulking procedure were used for screening of 1160 drugs with the aim to evaluate patterns of efficacy in the urachal cancer cells.

Results: Dose response data from the enzymatic cell viability assay and the image-based assay of 2D cell cultures showed the best consistency. With 3D cell culture conditions, the proliferation rate of the tumor cells was slower and potency of several drugs was reduced even following growth rate normalization of the responses. MEK, mTOR, and MET inhibitors were identified as the most cytotoxic targeted drugs. Secondary validation analyses confirmed the efficacy of these drugs also with the new human urachal adenocarcinoma cell line (MISB18) established from the patient's tumor.

Conclusions: All the tested ex vivo drug screening methods captured the patient's tumor cells' sensitivity to drugs that could be associated with the oncogenic KRASG12V mutation found in the patient's tumor cells. Specific drug classes however resulted in differential dose response profiles dependent on the used cell culture method indicating that the choice of assay could bias results from ex vivo drug screening assays for selected drug classes.

Keywords: Ex vivo drug screening; Precision medicine; Rare cancer; Urachal carcinoma.

Publication types

  • Comparative Study

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / genetics
  • Adenocarcinoma / pathology
  • Adult
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Cystectomy
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor / methods
  • Enzyme Assays / methods
  • Feasibility Studies
  • Humans
  • Male
  • Mitogen-Activated Protein Kinase Kinases / antagonists & inhibitors
  • Mutation
  • Precision Medicine / methods*
  • Primary Cell Culture / methods
  • Proto-Oncogene Proteins c-met / antagonists & inhibitors
  • Proto-Oncogene Proteins p21(ras) / genetics
  • Reproducibility of Results
  • TOR Serine-Threonine Kinases / antagonists & inhibitors
  • Urachus / pathology
  • Urachus / surgery
  • Urinary Bladder Neoplasms / drug therapy*
  • Urinary Bladder Neoplasms / genetics
  • Urinary Bladder Neoplasms / pathology


  • Antineoplastic Agents
  • KRAS protein, human
  • MTOR protein, human
  • MET protein, human
  • Proto-Oncogene Proteins c-met
  • TOR Serine-Threonine Kinases
  • Mitogen-Activated Protein Kinase Kinases
  • Proto-Oncogene Proteins p21(ras)

Supplementary concepts

  • Urachal adenocarcinoma

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