Lung Cancer Organoids

Lung cancer is the leading cause of cancer deaths worldwide. Lung cancer is histologically diverse, including three major types (small cell carcinoma, squamous cell carcinoma and adenocarcinoma) and several uncommon types (such as adenosquamous carcinoma and large cell neuroendocrine carcinoma). Lung cancer shows substantial genetic and phenotypic heterogeneity across individuals, driving the demand for personalized medicine.

Current models for lung cancer include two-dimensional (2D) and three-dimensional (3D) cell culture systems, as well as patient-derived mouse xenografts (PDX). Patient-derived cells can be isolated from tumor biopsies and used in in vitro tumor models to track disease progression and screen chemotherapeutics. However, isolating a pure population of cancer cells eliminates many non-tumor cell components that maintain or support tumor progression, such as stromal cells or extracellular matrix components (ECM). PDX model aims to alleviate these concerns by creating a microenvironment in which the behavior of cells may be more similar to those in physiological conditions. However, they lack both human and cancer-specific components, which may change the behavior of human cancer cells. Considering these limitations, ex vivo 3D cell culture model has aimed to create microenvironments containing specific ECM and stromal components to best replicate disease behavior and progression. The 3D cell culture system provides a promising opportunity for drug screening and drug development.

As a preclinical model, organoids are beneficial for patient-specific treatment due to their ability to maintain important biological and structural characteristics of native tissues. The development of an in vitro test platform capable of providing a physiologically suitable microenvironment and producing 3D organoids with controllable size can help predict the precise drug response of disease. OrganoLab has been able to use tumor cells from lung cancer patients to create organoids that display in-vivo-like anatomy and drug response and thus could serve as more accurate disease models for studying tumor progression and drug development. We established organoids from patient tissues comprising five histological subtypes of lung cancer as in vitro models representing individual patient. Our lung cancer organoids outline the tissue architecture of the primary lung tumors and maintain the genomic alterations of the original tumors during long-term expansion in vitro.

References

1. Huo, Ku-Geng; et al.; Patient-derived cell line, xenograft and organoid models in lung cancer therapy. Translational Lung Cancer Research, 2020, 9(5): 2214-2232.
2. Mazzocchi, A. et al.; Pleural Effusion Aspirate for Use in 3D Lung Cancer Modeling and Chemotherapy Screening. ACS Biomaterials Science & Engineering, 2019, 5(4): 1937-1943.
3. Kim, M. et al.; Patient-derived lung cancer organoids as in vitro cancer models for therapeutic screening. Nat Commun. 2019, 10(1): 3991.
4. Jung, Da Jung; et al.; A one-stop microfluidic-based lung cancer organoid culture platform for testing drug sensitivity. Lab on a Chip, 2019, 19: 2854-2865.
5. Yamanishi, C. et al.; Techniques to Produce and Culture Lung Tumor Organoids. Tumor Organoids, 2017, 1-15.