3D Breast Tumor Models for Radiobiology Applications

Abstract

Breast cancer is a leading cause of cancer-associated death in women. The clinical management of breast cancers is normally carried out using a combination of chemotherapy, surgery and radiation therapy. The majority of research investigating breast cancer therapy until now has mainly utilized two-dimensional (2D) in vitro cultures or murine models of disease. However, there has been significant uptake of three-dimensional (3D) in vitro models by cancer researchers over the past decade, highlighting a complimentary model for studies of radiotherapy, especially in conjunction with chemotherapy. In this review, we underline the effects of radiation therapy on normal and malignant breast cells and tissues, and explore the emerging opportunities that pre-clinical 3D models offer in improving our understanding of this treatment modality.

Use of 3D Spheroid Models for the Assessment of RT Response in Head and Neck Cancer

“…Although 3D models, such as spheroids, have proven to be a tool to bridge the gap between 2D and in vivo models in precision medicine [ 10 ], in the radiobiology field, data comparing 3D in vitro models to in vivo models are limited. Hence, we assessed whether we could recapitulate the RT response seen in 3D spheroids ( Figure 2 A,B) in vivo by comparing the growth curves of HPV-negative CAL27 and HPV-positive SCC154 spheroids with in vivo tumor growth curves of the same cell lines ( Figure 3 B).…”

“…Preclinical models resembling human tumors are essential to understand the biological mechanisms of cancer formation and therapy response. In the field of radiation biology, clonogenic radiation survival curves, in which the number of surviving clones are measured, are the gold standard to determine the relative radiosensitivity of cells or to determine the effect of drug treatments [ 10 ]. This is because clonogenic survival assays are an efficient, practical and low-cost model [ 11 , 12 , 13 , 14 ].…”

“…Sharing the simplicity and efficiency of 2D cultures, 3D models more accurately represent the dynamic tumoral architecture, including typical features such as naturally occurring hypoxic regions and cell–cell interactions [ 13 , 16 ]. Although these features are important factors in determining the RT response, the use of 3D models in the field of radiobiology is still limited [ 10 ].…”

Radiotherapy on-chip: microfluidics for translational radiation oncology

“…[120][121][122] Organs-on-a-chip are versatile in vitro tools to recapitulate the structure and behavior of different tissues, that can easily be integrated into radiobiological studies. 22,23,25,120,123,124 For example, one group investigated the radiation response of different tissues, including the gut and bone-marrow, on chip (Fig. 4B).…”

Characterisation of 3D Bioprinted Human Breast Cancer Model for In Vitro Drug and Metabolic Targeting

“…Therefore, several new 3D breast cancer models have started to be used widely in different experiments [32,33]. These models highlight changes in cell behaviour between cancer cell growth in 2D and 3D models, including altered proliferation, gene expression, and chemo-and radiosensitivity [34,35]. Therefore, the goal of 3D models is to retain cellular behaviour as closely as possible to that of in vivo tissues and simultaneously preserve investigational possibilities, studying signalling alterations and tumour development with regard to drug responsiveness in particular.…”