Fig. 5

Fundamental preclinical models for SCLC research. Preclinical research commonly relies on well-established assays based on two-dimensional (2D) or three-dimensional (3D) cell culture. Different cell compositions (cell lines, circulating tumor cells, tissues) can be furthermore examined in vivo via subcutaneous or orthotopic transplantation. Hence, CDX or PDX xenotransplantation mimic human disease regardless of immune microenvironment. The genetically engineered mouse model (GEMM) displays a platform to investigate tumor initiation and tumorigenesis of SCLC via genetic knock-out. In contrast, humanized mice present intact immunologic features that may be exploited to investigate the interaction between SCLC tumors and their microenvironment. Zebrafish larvae are frequently utilized to study the dynamic invasion of tumor cells in vivo or evaluate cost-effective chemical screenings. Sampling of representative tissue samples is rather rare in SCLC patients due to infrequently performed surgery. Rapid research autopsies should be used with greater frequency in SCLC research. Created with BioRender.com. CDX - Cell-derived xenograft; PDX – Patient-derived xenograft; GEMM – Genetically engineered mouse model