Our recent discovery of conditional reprogramming (CR) to generate cell cultures from human tissues offers new and exciting opportunities for biospecimen repositories. This cell technology makes it possible to rapidly generate cell cultures from surgical specimens and small biopsies, thereby providing an unlimited amount of patient material for genetic and proteomic analysis. However, this technology goes further: it will allow the functional analysis of tumor cells and comparison with the patients' normal cells from the same tissue. In this proposal we will extend and validate aspects of the CR technology and optimize its usage for biobanking. It is important to verify that the genotype and functional responses of CR cells mimics that of the primary tumor and experiments will address these issues using exome sequencing and TruSeq analysis. We will also examine whether the CR cells can predict patient responses to therapies, as we have recently described for a single case in the New England Journal of Medicine. Indeed, we believe that this technology will alter how Pathology departments and tissue repositories freeze patient specimens. Rather than simply quick freezing samples for future molecular analysis, tumor samples will be frozen in cryopreservative, which will additionally permit the generation of cell cultures for diagnostic and therapeutic evaluation.
Earlier this year we published as study showing that it is now possible to establish cell cultures from normal and tumor tissue of cancer patients and to expand them rapidly and efficiently so that they can be used for diagnostic and therapeutic purposes. The intent of this proposal is to optimize and standardize this system so that it can be used by many medical centers for storing and studying a patient's tumor. This method not only provides unlimited material for oncologists to study, but it represents a potential new approach for truly personalized medicine.
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