3D cancer models: One step closer to in vitro human studies

Abstract

Cancer immunotherapy is the great breakthrough in cancer treatment as it displayed prolonged progression-free survival over conventional therapies, yet, to date, in only a minority of patients. In order to broad cancer immunotherapy clinical applicability some roadblocks need to be overcome, first among all the lack of preclinical models that faithfully depict the local tumor microenvironment (TME), which is known to dramatically affect disease onset, progression and response to therapy. In this review, we provide the reader with a detailed overview of current 3D models developed to mimick the complexity and the dynamics of the TME, with a focus on understanding why the TME is a major target in anticancer therapy. We highlight the advantages and translational potentials of tumor spheroids, organoids and immune Tumor-on-a-Chip models in disease modeling and therapeutic response, while outlining pending challenges and limitations. Thinking forward, we focus on the possibility to integrate the know-hows of micro-engineers, cancer immunologists, pharmaceutical researchers and bioinformaticians to meet the needs of cancer researchers and clinicians interested in using these platforms with high fidelity for patient-tailored disease modeling and drug discovery.

Metformin-Loaded Hyaluronic Acid-Derived Carbon Dots for Targeted Therapy against Hepatocellular Carcinoma by Glutamine Metabolic Reprogramming

“…In the recent past, 3D cell culture system has been used as an ideal model that recapitulates the tumor microenvironment (TME) more realistically and has the ability to mimic the biochemical and biomechanical signals involved in tumor cell growth and progression. , Herein, 3D tumor models have gained considerable attention over the years as they can be utilized to bridge the gap between in vitro experiments and in vivo studies prior to proceeding with clinical trials. , In the present study, an HCC tumor spheroid model was produced by culturing Hep3B cells in a 3D culture unit by utilizing the Hanging drop method. Bright field images of the tumor spheroids so obtained after 72 h of culture revealed the initial size of the spheroid to be of 180 μm and grew to about 690 μm in 72 h exhibiting spherical shape and high cell–cell connectivity (Figure a).…”

Adhesion, metastasis, and inhibition of cancer cells: a comprehensive review

“…To implement these findings in the clinic, overcoming challenges related to the tumor microenvironment and preclinical models is essential [ 55 , 56 ]. Furthermore, investigating the mechanisms of vascular and lymphatic invasion can offer insights into organ-specific metastasis patterns and may lead to strategies to disrupt the dissemination process [ 55 ].…”

“…To implement these findings in the clinic, overcoming challenges related to the tumor microenvironment and preclinical models is essential [ 55 , 56 ]. Furthermore, investigating the mechanisms of vascular and lymphatic invasion can offer insights into organ-specific metastasis patterns and may lead to strategies to disrupt the dissemination process [ 55 ]. Additionally, exploring epigenetic regulation and chromatin remodeling in metastatic cells may unveil potential epigenetic therapies to reprogram metastatic cells’ behavior [ 56 ].…”

Protocol to generate scaffold-free, multicomponent 3D melanoma spheroid models for preclinical drug testing

“… 3 , 4 Their high reproducibility allows upscaling to high-throughput drug screening for drug discovery as well as studies investigating the mechanisms of drug responses. 5 , 6 , 7 , 8 , 9 , 10 , 11 …”