Patient-Derived Lung Tumoroids—An Emerging Technology in Drug Development and Precision Medicine

Abstract

Synthetic 3D multicellular systems derived from patient tumors, or tumoroids, have been developed to complete the cancer research arsenal and overcome the limits of current preclinical models. They aim to represent the molecular and structural heterogeneity of the tumor micro-environment, and its complex network of interactions, with greater accuracy. They are more predictive of clinical outcomes, of adverse events, and of resistance mechanisms. Thus, they increase the success rate of drug development, and help clinicians in their decision-making process. Lung cancer remains amongst the deadliest of diseases, and still requires intensive research. In this review, we analyze the merits and drawbacks of the current preclinical models used in lung cancer research, and the position of tumoroids. The introduction of immune cells and healthy regulatory cells in autologous tumoroid models has enabled their application to most recent therapeutic concepts. The possibility of deriving tumoroids from primary tumors within reasonable time has opened a direct approach to patient-specific features, supporting their future role in precision medicine.

Intratumoral injection of melatonin enhances tumor regression in cell line-derived and patient-derived xenografts of head and neck cancer by increasing mitochondrial oxidative stress

“…On the other hand, we must consider the genetic and epigenetic differences between cell lines and original tumors, which make it difficult to evaluate how much of the original tumor biology is retained in established cell line models that have been maintained long-term in vitro [19,20,57]. However, culturing cancer cells from human solid tumors has generally not been rapid or readily feasible because biopsy material is usually scant and it is difficult to eliminate CAFs [57].…”

“…The PDC obtained from a human biopsy of head and neck cancer tissue are referred to here as sample 1 (SP1) [23]. Primary HNSCC cells require specific culture medium and conditions to avoid cancer-associated fibroblast (CAF) overgrowth [20]. PNEU-medium provides a selection advantage to epithelial tumor cells and facilitates their proliferation so that they are not overgrown by CAFs [23].…”

“…Nevertheless, these models have important limitations, as they only represent a subpopulation of the original tumor and are largely homogenous [18]. Interestingly, patient-derived tumor models reflect the heterogeneity of real patient tumor tissues [19] and encompass multiple factors, such as histological structures, malignant genotypes, and phenotypes [20]. Therefore, patient-derived tumor xenografts (PDXs) are a better alternative for studying cancer biology and drug sensitivity [18].…”

Organoid factory: The recent role of the human induced pluripotent stem cells (hiPSCs) in precision medicine

“…Thus, having a co-culture of tumor cells together with fibroblasts and immunocytes could help achieve a higher fidelity platform. Quéméneur and others, indeed, successfully included fibroblasts and macrophages in a patient-derived tumoroid observing an enrichment in immune cells and obtaining the expression of the markers of lung adenocarcinoma ( Lê et al, 2022 ). These flourishing examples are paving the way for the use of tumoroid cultures in clinical trials as well as for basic research.…”

Vascularized patient-derived tumoroids supplemented with immune cells to predict response towards treatment for lung cancer patients

“…As mentioned in our previous review, some limitations have been reported in the described lung cancer organoids (e.g., lack of cell types from the tumor microenvironment (TME)). To better optimize this, the use of autologous peripheral blood immune cells (PBMCs) will permit to maintain the TME complexity in vitro 21 . Co-culture of PDTs with PBMCs permit to address several points: (i) in ltration and tra cking in PDTs, and (ii) cytotoxicity activity of autologous immune cells.…”