Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

Ex Vivo Drug Testing of Patient-Derived Lung Organoids to Predict Treatment Responses for Personalized Medicine

Version 1 : Received: 15 June 2023 / Approved: 16 June 2023 / Online: 16 June 2023 (08:42:28 CEST)

How to cite: Hung, C.; Williams, M.; Williams, R.; Chen, M.; Kamali, S.; Sambandam, V.; Chiu, C.H.; Osmulski, P.; Gaczynska, M.; DeArmond, D.; Gaspard, C.; Macini, M.; Song, L.; Jin, L.; Schiavini, P.; Chen, C.; Taverna, J. Ex Vivo Drug Testing of Patient-Derived Lung Organoids to Predict Treatment Responses for Personalized Medicine. Preprints 2023, 2023061176. https://doi.org/10.20944/preprints202306.1176.v1 Hung, C.; Williams, M.; Williams, R.; Chen, M.; Kamali, S.; Sambandam, V.; Chiu, C.H.; Osmulski, P.; Gaczynska, M.; DeArmond, D.; Gaspard, C.; Macini, M.; Song, L.; Jin, L.; Schiavini, P.; Chen, C.; Taverna, J. Ex Vivo Drug Testing of Patient-Derived Lung Organoids to Predict Treatment Responses for Personalized Medicine. Preprints 2023, 2023061176. https://doi.org/10.20944/preprints202306.1176.v1

Abstract

Lung cancer is the leading cause of global cancer-related mortality resulting in ~1.8 million deaths annually. Systemic, molecular targeted, and immune therapies have provided significant improvements of survival outcomes for patients. However, drug resistance usually arises and there is an urgent need for novel therapy screening and personalized medicine. 3D patient-derived organoid (PDO) models have emerged as a more effective and efficient alternative for ex vivo drug screening than 2D cell culture and patient-derived xenograft (PDX) models. In this review, we performed an extensive search of lung cancer PDO-based ex vivo drug screening studies. Lung cancer PDOs were successfully established from fresh or biobanked sections/biopsy of lung tumors, PDXs, and pleural affusion. PDOs were subject to ex vivo drug screening with chemotherapy, targeted therapy and immune therapy agents. PDOs mainly recapitulated the genomic alterations, transcriptomic landscape and drug sensitivity of primary tumors. Although sample sizes of the previous studies were limited and some technical challenges remained, PDOs showed promise to screen novel therapy drugs. With the technical advance of high throughput, tumor-on-chip, combined microenvironment, and air-liquid interface (ALI), the drug screening using PDOs would serve better for precision care of lung cancer patients.

Keywords

lung cancer; organoid; drug screening; high throughput; translational; pre-clinical; clinical; tumor microenvironment; personalized medicine

Subject

Medicine and Pharmacology, Oncology and Oncogenics

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