Lung Cancer Organoids: The Rough Path to Personalized Medicine

Abstract

Lung cancer is the leading cause of cancer death worldwide. Despite significant advances in research and therapy, a dismal 5-year survival rate of only 10-20% urges the development of reliable preclinical models and effective therapeutic tools. Lung cancer is characterized by a high degree of heterogeneity in its histology, a genomic landscape, and response to therapies that has been traditionally difficult to reproduce in preclinical models. However, the advent of three-dimensional culture technologies has opened new perspectives to recapitulate in vitro individualized tumor features and to anticipate treatment efficacy. The generation of lung cancer organoids (LCOs) has encountered greater challenges as compared to organoids derived from other tumors. In the last two years, many efforts have been dedicated to optimizing LCO-based platforms, resulting in improved rates of LCO production, purity, culture timing, and long-term expansion. However, due to the complexity of lung cancer, further advances are required in order to meet clinical needs. Here, we discuss the evolution of LCO technology and the use of LCOs in basic and translational lung cancer research. Although the field of LCOs is still in its infancy, its prospective development will likely lead to new strategies for drug testing and biomarker identification, thus allowing a more personalized therapeutic approach for lung cancer patients.

Keywords: drug testing; lung cancer; organoids; personalized medicine; preclinical models; targeted therapy.

Figure 1

Timetable of landmark studies that have contributed to the generation of 3D cultures of lung epithelial cells. LCOs, lung cancer organoids; SCLC, small-cell lung cancer; NSCLC, non-small-cell lung cancer; PDX, patient-derived xenograft [9,16,17,22,23,24,25,27,32,34,35,37,38,39,40,42,44,58,59,60].

Figure 2

Applications of LCOs in basic and translational lung cancer research. TME, tumor microenvironment; LCOs, lung cancer organoids; ADCs, antibody-drug conjugates; ICIs, immune checkpoint inhibitors; ALI, air–liquid interface; LUAD, lung adenocarcinoma; LUSC, lung squamous cell carcinoma; PDX, patient-derived xenograft. Others: adenoid cystic carcinoma, sarcomatoid carcinoma, atypical carcinoid, mucoepidermoid carcinoma, large-cell neuroendocrine carcinoma. Not all the relevant references were reported in the figure due to space issues; we apologize to the authors who we were unable to cite [16,17,34,35,39,40,41,45,50,57,58,59,60,61,63,65,74].