From clinical specimens to human cancer preclinical models—a journey the NCI‐cell line database—25 years later

Abstract

The intramural the National Cancer Institute (NCI) and more recently the University of Texas Southwestern Medical Center with many different collaborators comprised a complex, multi‐disciplinary team that collaborated to generated large, comprehensively annotated, cell‐line related research resources which includes associated clinical, and molecular characterization data. This material has been shared in an anonymized fashion to accelerate progress in overcoming lung cancer, the leading cause of cancer death across the world. However, this cell line collection also includes a range of other cancers derived from patient‐donated specimens that have been remarkably valuable for other types of cancer and disease research. A comprehensive analysis conducted by the NCI Center for Research Strategy of the 278 cell lines reported in the original Journal of Cellular Biochemistry Supplement, documents that these cell lines and related products have since been used in more than 14 000 grants, and 33 207 published scientific reports. This has resulted in over 1.2 million citations using at least one cell line. Many publications involve the use of more than one cell line, to understand the value of the resource collectively rather than individually; this method has resulted in 2.9 million citations. In addition, these cell lines have been linked to 422 clinical trials and cited by 4700 patents through publications. For lung cancer alone, the cell lines have been used in the research cited in the development of over 70 National Comprehensive Cancer Network clinical guidelines. Finally, it must be underscored again, that patient altruism enabled the availability of this invaluable research resource.

SCLC-CellMiner: A Resource for Small Cell Lung Cancer Cell Line Genomics and Pharmacology Based on Genomic Signatures

“…Yet TCGA was not extended to SCLC, because of a lack of readily accessible and adequate tumor tissue, as most patients are diagnosed by fine-needle aspiration. Nevertheless, SCLC research has benefited from the systematic collection of a large number of tumor cell lines, most of them developed at the NCI in the NCI-VA and NCI-Navy Medical Oncology Branches ( Mulshine et al, 2019 ). This collection has been distributed widely and included in the cancer drug genomic databases of the NCI, Broad Institute/MIT, and Sanger/Massachusetts General Hospital (MGH) ( Barretina et al, 2012 ; Garnett et al, 2012 ; Iorio et al, 2016 ; Polley et al, 2016 ).…”

In vivo and in vitro cell based model of lung adenocarcinoma from patients with pleural effusion

“…A number of studies for identification and isolation of CSCs from NSCLC has been focused on these minority cell subsets utilizing cell surface glycoproteins CD133 and CD44 of in vitro established cell lines [20,[44][45][46][47][48]. However, expression of these molecules is variable in various LC cell lines and contradictory results were obtained in these studies, possible due to shortcomings inherent to in vitro propagated cells [19,20].…”

“…This requirement has been met to a certain degree by systematic in vitro establishment of cancer cell lines obtained from a number of laboratories and deposited in the American Type Culture Collection (ATCC) [19,20]. In case of LC cell lines, over 75% originated from the National Cancer Institute (Bethesda, Maryland) and Hamon Cancer Center (Dallas, Texas) [19].…”

“…In case of LC cell lines, over 75% originated from the National Cancer Institute (Bethesda, Maryland) and Hamon Cancer Center (Dallas, Texas) [19]. Several of these LC cell lines were also included in the lung cancer cell line panel that had been characterized at molecular level [19,20]. This scale of human tumor material for research has been considerably enlarged by development of patient-derived xenografts (PDX).…”

“…These models enable one to study molecular mechanisms of tumor growth, the potential response of patients to anticancer therapy and drug resistance [19][20][21][22] and generated exceptional accumulation of basic knowledge of the cellular and molecular biology of the disease [15,[20][21][22][23][24]. Despite the extensive progress in LC models [20,25,26], recent reports using newly established LAC cell lines have challenged some recent observations related to CSCs as well as earlier theories about the epithelial-mesenchymal transition (EMT) process [27,28]. Taking into consideration extensive heterogeneity of LAC, additional expansion of in vitro and in vivo models can substantially contribute to our understanding of this severe form of malignancy.…”