Mimicking the Complexity of Solid Tumors: How Spheroids Could Advance Cancer Preclinical Transformative Approaches

Cancers (Basel). 2025 Mar 30;17(7):1161. doi: 10.3390/cancers17071161.

Abstract

Traditional 2D cell culture models present significant limitations in replicating the intricate architecture and microenvironment of in vivo solid tumors, which are essential for accurately studying cancer initiation, growth, progression, and metastasis. This underscores the need for the development of advanced preclinical models to accelerate research outcomes. Emerging 3D cell culture systems, particularly spheroid models, provide a more realistic representation of solid tumor properties by capturing the complex interactions occurring within the tumor microenvironment, including the extracellular matrix dynamics that influence cancer progression. Among solid tumors, breast cancer remains the most frequently diagnosed cancer among women globally and a leading cause of cancer-related mortality. Here we emphasize the value of breast cancer cell-derived spheroids in revealing differential molecular characteristics and understanding cancer cell properties during the early stages of invasion into adjacent tissues. Conclusively, this study underscores the urgent need to adopt 3D cell culture platforms, given their significant contributions to advanced cancer research and pharmaceutical targeting. This may well offer a transformative approach for preclinical studies and enhance our ability to test therapeutic efficiency in conditions that closely mimic the growth and progression of in vivo solid tumors.

Keywords: 3D cell culture models; matrix-independent models; solid tumors; spheroids.