Applications of lung cancer organoids in precision medicine: from bench to bedside

Cell Communication and Signaling (2023) 21:350 Li et al. Cell Communication and Signaling https://doi.org/10.1186/s12964-023-01332-9 Open Access REVIEW Applications of lung cancer organoids in precision medicine: from bench to bedside Huihui Li1,2†, Zexin Chen3†, Ning Chen1,4, Yun Fan1,2*†, Yaping Xu5*† and Xiaoling Xu5,2*† Abstract As the leading cause of cancer-related mortality, lung cancer continues to pose a menacing threat to human health worldwide. Lung cancer treatment options primarily rely on chemoradiotherapy, surgery, targeted therapy, or immunotherapy. Despite significant progress in research and treatment, the 5-year survival rate for lung cancer patients is only 10–20%. There is an urgent need to develop more reliable preclinical models and valid therapeutic approaches. Patient-derived organoids with highly reduced tumour heterogeneity have emerged as a promising model for highthroughput drug screening to guide treatment of lung cancer patients. Organoid technology offers a novel platform for disease modelling, biobanking and drug development. The expected benefit of organoids is for cancer patients as the subsequent precision medicine technology. Over the past few years, numerous basic and clinical studies have been conducted on lung cancer organoids, highlighting the significant contributions of this technique. This review comprehensively examines the current state-of-the-art technologies and applications relevant to the formation of lung cancer organoids, as well as the potential of organoids in precision medicine and drug testing. † Huihui Li and Zexin Chen these authors have contributed equally to this work as co-first authors. † Yun Fan, Yaping Xu and Xiaoling Xu these authors have contributed equally to this work as co-corresponding authors. *Correspondence: Yun Fan Yaping Xu Xiaoling Xu 1 Department of Medical Thoracic Oncology, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou 310022, Zhejiang, China 2 Postgraduate Training Base Alliance, Wenzhou Medical University, Wenzhou 325035, Zhejiang, China 3 Guangdong Research Center of Organoid Engineering and Technology, Guangzhou 510535, Guangdong, China 4 Department of Oncology, The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou 310053, China 5 Department of Radiation Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China Background Lung cancer is currently the most common type of cancer worldwide, with the highest mortality rate compared to other forms of cancer. It accounts for approximately 11.4% of all cancer cases and 18.0% of cancer-related deaths worldwide [1]. To provide sufficient decisionmaking evidence and judge prognosis, emerging methods such as genomics and microbiomics should be actively applied in addition to traditional diagnostic methods. The core of precision medicine involves diagnosis through underlying molecular analysis methods such as genetic testing. This allows for development of novel therapeutic avenues that differ from surgery and chemotherapy, including targeted therapy based on specific tumor driver genes and immunotherapy based on tumour mutational burden (TMB) [2]. In recent years, notable progress has been made in the field of targeted anticancer drugs and immunotherapy for lung cancer, but challenges regarding drug efficacy, toxicity and drug resistance remain. For example, lung adenocarcinoma exhibits marked inter- and intratumoral heterogeneity, which may lead to treatment failure © The Author(s) 2023. 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The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Li et al. Cell Communication and Signaling (2023) 21:350 and resistance development [3]. Therefore, it is crucial to design in vivo and in vitro model systems that can precisely imitate tumours to effectively analyse tumour in vitro culture, cell types, and drug sensitivity. The use of two-dimensional (2D) cell culture is widespread in lung cancer research for drug screening purposes, however, it does not encompass the in vivo tumor microenvironment (TME) [4]. A accumulation of genetic and epigenetic aberrations [5] during the in vitro process may negatively impact the culture of stem cells and diversity of cell types [6]. While human cancer cells that have been cultured in 2D and immortalized lose their phenotypic and genetic variability, tumour xenografts derived from patients (PDX) can largely preserve the original tumour’s heterogeneity [7]. It presents a potential platform for testing the effectiveness of personalized anticancer drugs in drug screening and the development of new drugs. However, this approach is not suitable for large-scale drug discovery screening due to its high cost and time consumption. As a result, endeavors have been made to produce patient-derived organoids (PDOs), a three-dimensional (3D) in vitro model. The model manifests molecular and morphological characteristics that are more akin to those Page 2 of 13 in vivo when compared to 2D cell culture. Over the past decade, numerous studies have initiated assessment of anticancer medication using PDOs as a viable approach to determine optimal drugs for patients who satisfy multiple treatment requirements. This review focuses on the comparison of PDO models with traditional cell lines and PDX models, with a detailed explanation of the usage, constraints, and future outlook of lung cancer PDOs. Overview of lung cancer organoid models Organoids are in vitro 3D mini "organs" that highly mimic the pathophysiological system of the human body and can be created from embryonic stem cells (ESCs) [8], spermatogonial stem cells (SSCs) [9], and pluripotent stem cells (iPSCs) [10]. Through a self-assembly process, these organoids form with the aid of the stemness of cells sourced from a patient. While the in vitro culture of animal cells and organs has been a topic of scientific concern for almost a century, the f (...truncated)