Patient-derived tumor spheroid cultures as a promising tool to assist personalized therapeutic decisions in breast cancer

Abstract

Background Breast cancer is the most common cause of cancer related deaths in women. Treatment of breast cancer has many limitations including a lack of accurate biomarkers to predict success of chemotherapy and intrinsic resistance of a significant group of patients to the gold standard of therapy. Therefore, new tools are needed to provide doctors with guidance in choosing the most effective treatment plan for a particular patient and thus to increase the survival rate for breast cancer patients. Methods Here, we present a successful method to grow in vitro spheroids from primary breast cancer tissue. Samples were received in accordance with relevant ethical guidelines and regulations. After tissue dissociation, in vitro spheroids were generated in a scaffold-free 96-well plate format. Spheroid composition was investigated by immunohistochemistry (IHC) of epithelial [pan cytokeratin (panCK)], stromal (vimentin) and breast cancer-specific markers (ER, PR, HER2, GATA). Growth and cell viability of the spheroids were assessed upon treatment with multiple anti-cancer compounds. Student’s t -test and two-way ANOVA test were used to determine statistical significance. Results We were able to successfully grow spheroids from 27 out of 31 samples from surgical resections of breast cancer tissue from previously untreated patients. Recapitulation of the histopathology of the tissue of origin was confirmed. Furthermore, a drug panel of standard first-line chemotherapy drugs used to treat breast cancer was applied to assess the viability of the patient-derived spheroids and revealed variation between samples in the response of the spheroids to different drug treatments. Conclusions We investigated the feasibility and the utility of an in vitro , patient-derived spheroid model for breast cancer therapy, and we conclude that spheroids serve as a highly effective platform to explore cancer therapeutics and personalized treatment efficacy. These results have significant implications for the application of this model in clinical personalized medicine.

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

“…[65,[68][69][70][71][72]. Modelling the complexity of tumour progression, especially the steps of metastasis formation, also requires microfluidics and several host tissues to be combined in novel in vitro test systems [82][83][84][85][86][87][88][89][90][91][92][93]. The continuously emerging data about such devices for BC and more complex BC models were summarised by Moccia and Haase [94,95].…”

Role of three-dimensional cell culture in therapeutics and diagnostics: an updated review

“…They successfully developed a 3D model using patients’ tissue and confirmed the recapitulation of the tissue’s original histopathology by techniques such as immunohistochemistry. Moreover, a standard chemotherapeutic drug panel was also tested on these cell cultures and showed its tremendous efficacy and proved the variation in different cancer cells [ 15 ]. A recent study also showed the efficacy of this technique which produced pluripotent stem cells which had uniform size and shape and also increased gene expression and functionality [ 16 ].…”

Multicellular Tumor Spheroids in Nanomedicine Research: A Perspective

“…This method is very useful for generating uniform spheroids with a designated size and shape, even though long-term culture and media replacement remain a challenge ( 18 ). To overcome these limitations, companies have developed and commercialized different plates, such as Akura™ PLUS and Perfecta3D®, that simplify the culture procedures ( 19 , 20 ).…”