Ex Vivo Treatment Response of Primary Tumors and/or Associated Metastases for Preclinical and Clinical Development of Therapeutics |
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Authors: | Adriana D. Corben Mohammad M. Uddin Brooke Crawford Mohammad Farooq Shanu Modi John Gerecitano Gabriela Chiosis Mary L. Alpaugh |
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Affiliation: | 1Department of Pathology, Memorial Sloan Kettering Cancer Center;2Molecular Pharmacology and Chemistry Program, Memorial Sloan Kettering Cancer Center;3Department of Radiology, Weill Cornell Medical College;4Department of Medicine, Memorial Sloan Kettering Cancer Center;5Department of Oncology, Memorial Sloan Kettering Cancer Center;6Department of Surgery, Memorial Sloan Kettering Cancer Center |
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Abstract: | The molecular analysis of established cancer cell lines has been the mainstay of cancer research for the past several decades. Cell culture provides both direct and rapid analysis of therapeutic sensitivity and resistance. However, recent evidence suggests that therapeutic response is not exclusive to the inherent molecular composition of cancer cells but rather is greatly influenced by the tumor cell microenvironment, a feature that cannot be recapitulated by traditional culturing methods. Even implementation of tumor xenografts, though providing a wealth of information on drug delivery/efficacy, cannot capture the tumor cell/microenvironment crosstalk (i.e., soluble factors) that occurs within human tumors and greatly impacts tumor response. To this extent, we have developed an ex vivo (fresh tissue sectioning) technique which allows for the direct assessment of treatment response for preclinical and clinical therapeutics development. This technique maintains tissue integrity and cellular architecture within the tumor cell/microenvironment context throughout treatment response providing a more precise means to assess drug efficacy. |
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Keywords: | Cancer Biology Issue 92 Ex vivo sectioning Treatment response Sensitivity/Resistance Drug development Patient tumors Preclinical and Clinical |
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