Abstract
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.
Highlights
Traditional cancer models including cell lines and animal models have limited applications in both basic and clinical cancer research
Unlike cell lines, such as lack of stromal components, clonal selection, and genetic drift due to long-term culturing conditions, patient-derived xenografts (PDXs) models cross-talk between stromal components and epithelial tumor cells, appear to have high genetic stability, especially during early passages, and can preserve the molecular and cellular heterogeneity of the primary tumor
We will discuss the application of Conditionally Reprogrammed Cells (CRCs) technology in cancer research with a case with tongue squamous cell carcinoma (TSCC) as an example
Summary
Cancer research and drug development utilize cancer cell lines, their derived cancer models and genetically engineered mouse models (GEMM). The success rate of achieving this has been only 1–10% depending on the tissue type and model type [5] These cell lines have been useful for in vitro experiments to study cancer biology, biochemistry, and drug targets. The diagnosis and treatment decisions are based on the histopathological features, morphology and in some instances a restricted panel of immunohistochemical markers that are able to group patients in subgroups This approach fails to recognize the variations within each subgroup, leading to failure of therapy regimens and recurrence of tumor. Many human cancers develop after years of exposure to carcinogens from smoking and environment, and harbor multiple and diversified genetic alterations This at least partially explains that only approximately 5% of oncology drugs developed based on these models and entering clinical trials are eventually approved by the Food and Drug Administration [13]
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