Three-dimensional heterotypic colorectal cancer spheroid models for evaluation of drug response

Abstract

Colorectal cancer (CRC) is a leading cause of death worldwide. Improved preclinical tumor models are needed to make treatment screening clinically relevant and address disease mortality. Advancements in 3D cell culture have enabled a greater recapitulation of the architecture and heterogeneity of the tumor microenvironment (TME). This has enhanced their pathophysiological relevance and enabled more accurate predictions of tumor progression and drug response in patients. An increasing number of 3D CRC spheroid models include cell populations such as cancer-associated fibroblasts (CAFs), endothelial cells (ECs), immune cells, and gut bacteria to better mimic the in vivo regulation of signaling pathways. Furthermore, cell heterogeneity within the 3D spheroid models enables the identification of new therapeutic targets to develop alternative treatments and test TME-target therapies. In this mini review, we present the advances in mimicking tumor heterogeneity in 3D CRC spheroid models by incorporating CAFs, ECs, immune cells, and gut bacteria. We introduce how, in these models, the diverse cells influence chemoresistance and tumor progression of the CRC spheroids. We also highlight important parameters evaluated during drug screening in the CRC heterocellular spheroids.

Extracellular Vesicles Comprising Carborane Prepared by a Host Exchanging Reaction as a Boron Carrier for Boron Neutron Capture Therapy

“…Cancer spheroids have been used as a threedimensional (3D) tumor tissue model expressing tumor growth for drug screening. 106,107 Colon26 spheroids in the active growing phase were exposed to CB@EVs, CB@ liposome, and the L-BPA/fructose complex (0.1 ppm) and irradiated with a thermal neutron at KUR. BNCT activity was monitored at 1, 2, and 7 days postirradiation by the WST-8 assay.…”

Biomimetic Scaffolds—A Novel Approach to Three Dimensional Cell Culture Techniques for Potential Implementation in Tissue Engineering

“…One of the main advantages of using spheroids in cancer research is the ability to measure drug response. Multiple studies have been conducted involving spheroids derived from various types of cancer, including colorectal cancer [ 39 , 40 , 41 , 42 ], breast cancer [ 41 , 43 , 44 ], lung cancer [ 45 , 46 ], ovarian cancer [ 1 , 47 , 48 ] and even Ewing sarcoma cells [ 49 ]. It is important to note that 3D cultures, particularly spheroids, are a valuable and effective tool for studying cancer biology.…”

A Short Post-Reattachment Ultrasensitive Window of Time in Human Cancer Cells as Therapeutic Target of Prolonged Low-Dose Administration of Specific Compounds

“…We previously found that depending on the specific in vitro microenvironmental condition, cancer cells display different chemoresistance profiles. For instance, cells growing under adherent conditions are more sensitive compared to cells growing under suspension conditions [ 2 – 4 ]. On the other hand, cells growing in the absence of serum are more resistant compared to cells growing in the presence of serum [ 5 , 6 ].…”