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Conditional Reprogramming for Patient-Derived Cancer Models and Next-Generation Living Biobanks

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Department of Pathology, Center for Cell Reprogramming, Georgetown University Medical Center, Washington, DC 20057, USA
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Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC 20057, USA
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Department of Otorhinolaryngology-Head and Neck Surgery, University of Maryland, Baltimore, MD 21201, USA
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Department of Otorhinolaryngology-Head and Neck Surgery, Georgetown University Medical Center, Washington, DC 20057, USA
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Inova Translational Medicine Institute, Inova Health System, Fairfax, VA 22031, USA
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Department of Radiation Medicine, Georgetown University Medical Center, Washington, DC 20057, USA
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iCryobiol and iFuture Technologies, Shanghai 200127, China
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University of California at Davis, Sacramento, CA 95817, USA
*
Author to whom correspondence should be addressed.
Cells 2019, 8(11), 1327; https://doi.org/10.3390/cells8111327
Received: 2 September 2019 / Revised: 14 October 2019 / Accepted: 25 October 2019 / Published: 27 October 2019
Traditional cancer models including cell lines and animal models have limited applications in both basic and clinical cancer research. Genomics-based precision oncology only help 2–20% patients with solid cancer. Functional diagnostics and patient-derived cancer models are needed for precision cancer biology. In this review, we will summarize applications of conditional cell reprogramming (CR) in cancer research and next generation living biobanks (NGLB). Together with organoids, CR has been cited in two NCI (National Cancer Institute, USA) programs (PDMR: patient-derived cancer model repository; HCMI: human cancer model initiatives. HCMI will be distributed through ATCC). Briefly, the CR method is a simple co-culture technology with a Rho kinase inhibitor, Y-27632, in combination with fibroblast feeder cells, which allows us to rapidly expand both normal and malignant epithelial cells from diverse anatomic sites and mammalian species and does not require transfection with exogenous viral or cellular genes. Establishment of CR cells from both normal and tumor tissue is highly efficient. The robust nature of the technique is exemplified by the ability to produce 2 × 106 cells in five days from a core biopsy of tumor tissue. Normal CR cell cultures retain a normal karyotype and differentiation potential and CR cells derived from tumors retain their tumorigenic phenotype. CR also allows us to enrich cancer cells from urine (for bladder cancer), blood (for prostate cancer), and pleural effusion (for non-small cell lung carcinoma). The ability to produce inexhaustible cell populations using CR technology from small biopsies and cryopreserved specimens has the potential to transform biobanking repositories (NGLB: next-generation living biobank) and current pathology practice by enabling genetic, biochemical, metabolomic, proteomic, and biological assays, including chemosensitivity testing as a functional diagnostics tool for precision cancer medicine. We discussed analyses of patient-derived matched normal and tumor models using a case with tongue squamous cell carcinoma as an example. Last, we summarized applications in cancer research, disease modeling, drug discovery, and regenerative medicine of CR-based NGLB. View Full-Text
Keywords: conditionally reprogrammed cells; patient-derived cancer models; organoids; living biobanks conditionally reprogrammed cells; patient-derived cancer models; organoids; living biobanks
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Palechor-Ceron, N.; Krawczyk, E.; Dakic, A.; Simic, V.; Yuan, H.; Blancato, J.; Wang, W.; Hubbard, F.; Zheng, Y.-L.; Dan, H.; Strome, S.; Cullen, K.; Davidson, B.; Deeken, J.F.; Choudhury, S.; Ahn, P.H.; Agarwal, S.; Zhou, X.; Schlegel, R.; Furth, P.A.; Pan, C.-X.; Liu, X. Conditional Reprogramming for Patient-Derived Cancer Models and Next-Generation Living Biobanks. Cells 2019, 8, 1327.

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