Background: Nonresponse to chemotherapy in colorectal carcinoma (CRC) is still a clinical problem. For most established treatment regimens, no predictive biomarkers are available. Patient-derived tumor slice culture may be a promising ex vivo technology to assess the drug susceptibility in individual tumors.
Methods: Patient-derived slice cultures of CRC specimens were prepared according to a standardized protocol and treated with different concentrations of 5-fluorouracil (5-FU) and an adapted FOLFOX regimen (5-FU and oxaliplatin) to investigate histologic response. Additionally, a semi-automatized readout using fluorescent stain-specific segmentation algorithms for Image J was established to quantify changes in tumor proliferation. Nonresponse to chemotherapy was defined as persisting tumor cell proliferation.
Results: Slices treated with 5-FU showed lower tumor cell fractions and dose-dependent alterations of proliferating tumor cells compared with controls (1 μM, Δ +3%; 10 μM, Δ -9%; 100 μM, Δ -15%). Individual tumor samples were examined and differences in chemotherapy susceptibility could be observed. Untreated slice cultures contained an average tumor cell fraction of 31% ± 7%. For all samples, the histopathologic characteristics exhibited some degree of intratumoral heterogeneity with regard to tumor cell morphology and distribution. The original tumor matched the features found in slices at baseline and after 3 days of cultivation.
Conclusions: Patient-derived slice cultures may help to predict response to clinical treatment in individual patients with CRC. Future studies need to address the problem of tumor heterogeneity and evolution. Prospective correlation of ex vivo results with the clinical course of treated patients is warranted.
Keywords: Chemosensitivity; Colorectal carcinoma; Human organotypic slice cultures; Individualized therapy; Predictive test.
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