(C-117) Characterization of Vascularized Tumor Explants for Personalized Medicine

Introduction:: Available treatments for pancreatic ductal adenocarcinoma (PDAC), such as surgical resection, radiation, and chemotherapy, provide limited tumor control even when the disease is contained in the pancreas at diagnosis. A rapid methodology for testing surgical samples from PDAC patients would provide oncologists with a new tool for planning treatment strategies after the surgery (adjuvant setting) or when the cancer returns. Several ex vivo and in vitro approaches have been developed to deconstruct cancer and investigate responses to anti-cancer treatments, but they generally do not reproduce tumor heterogeneity or reliably predict treatment response.

Materials and Methods:: We propose to overcome current limitations in personalized medicine by integrating intact tumor tissue harvested from patients into a supporting tissue bed that includes appropriate matrix, stromal cells, and blood vessels with high reproducibility. These “vascularized tumor explants” (VTEs) provide a new tool for drug screening, allowing analysis of tumor drug sensitivity within days or weeks. Such timing would permit the selection of active therapies. To test feasibility, we compared drug responses of patient-derived xenografts (PDX) cultures with PDX-derived VTE cultured tumors and PDAC cell spheroids. PDX lines from patients who responded to adjuvant gemcitabine (GEM; a standard drug used for PDAC) chemotherapy and from non-responders were grown in immunodeficient mice. Fragments from the resected tumors were grown as VTEs. Each PDX was treated with GEM either ex vivo as VTEs cultures or in vitro as spheroids.

Results, Conclusions, and Discussions:: < ![if !supportLists] >o < ![endif] >Results

After four days of treatment, tumors were analyzed for cell apoptosis, proliferation, and viability. Our results show that VTE cultures provide more reliable drug resistance predictions than spheroid cultures, suggesting that VTEs recapitulate cancer heterogeneity and signaling pathways that play an essential role in cancer response to treatment. In figure 1-A, the results of VTE after one week of tumor culture are shown. The qualitative results of GEM effect on a responder cancer deconstructed as VTE are shown in Fig.1-B.


< ![if !supportLists] >o < ![endif] >Conclusions and Discussion

< ![if !supportLists] >· < ![endif] >Methodology for testing patient PDAC samples at the time of resection that can give oncologists a new tool for planning treatment strategy when the cancer returns.

< ![if !supportLists] >· < ![endif] >Valid and easy executive technology able to translate into clinical studies.

< ![if !supportLists] >· < ![endif] >By using harvested tumor fragments, we naturally include all components that are important in tumor biology – including those that have not yet been explicitly identified and can therefore not be included in a “synthetic” system.

< ![if !supportLists] >· < ![endif] >Ability to test many types of drugs on any type of cancer.




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