Tumor slice culture system to assess drug response of primary breast cancer

Abstract

BackgroundThe high incidence of breast cancer has sparked the development of novel targeted and personalized therapies. Personalization of cancer treatment requires reliable prediction of chemotherapy responses in individual patients. Effective selection can prevent unnecessary treatment that would mainly result in the unwanted side effects of the therapy. This selection can be facilitated by characterization of individual tumors using robust and specific functional assays, which requires development of powerful ex vivo culture systems and procedures to analyze the response to treatment.MethodsWe optimized culture methods for primary breast tumor samples that allowed propagation of tissue ex vivo. We combined several tissue culture strategies, including defined tissue slicing technology, growth medium optimization and use of a rotating platform to increase nutrient exchange.ResultsWe could maintain tissue cultures for at least 7 days without losing tissue morphology, viability or cell proliferation. We also developed methods to determine the cytotoxic response of individual tumors to the chemotherapeutic treatment FAC (5-FU, Adriamycin [Doxorubicin] and Cyclophosphamide). Using this tool we designated tumors as sensitive or resistant and distinguished a clinically proven resistant tumor from other tumors.ConclusionThis method defines conditions that allow ex vivo testing of individual tumor responses to anti-cancer drugs and therefore might improve personalization of breast cancer treatment.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2119-2) contains supplementary material, which is available to authorized users.

Spatial aspects of oncogenic signalling determine the response to combination therapy in slice explants from Kras‐driven lung tumours

“…NSCLC slices cultured on rotating incubation units, to ensure continuous oxygenation, were fragile and showed dynamic culture‐induced changes, most prominently altered proliferation and mTORC1 hyperactivation. Although previous reports showed sustained viability of clinical tumour slices for 4–14 days , these studies derived conclusions from the selective analysis of cultured slices, whereas we systematically compared neighbouring cultured and uncultured slices. Furthermore, our study is the first to deeply analyse intratumour oncogenic signalling, and shows that signalling and proliferation alterations take place prior to overt changes in viability.…”

“…Within the IMI‐PREDECT project (http://www.predect.eu), we developed a workflow for short‐term culture of tumour slices, and showed that organotypic supports and atmospheric oxygen are strict requirements for tissue viability . A number of other studies have shown that responses to cytotoxic agents or selected targeted compounds can be modelled in clinical tumour‐derived slices . However, the question remains of how the in situ spatial signalling heterogeneity affects the pharmacodynamics of signalling inhibitors.…”

Tumour-on-a-chip: microfluidic models of tumour morphology, growth and microenvironment

“…Primary tumour tissues from biopsy or surgical resection can be embedded in ECM and cultured as an in vitro model [30][31][32][33][34] (figure 2a). The embedded tumour sections retain the tumour vasculature, nearby stroma and the heterogeneity of the tumour cells.…”

Precision Oncology: The Road Ahead

“…soft, mucinous or fatty tissue), where firm tissue consistency is required [213, 214]. Another drawback of slice cultures is the loss of viability within 5 to 7 days [211].…”