Together with surgery and radiotherapy, chemotherapy is one of the main cancer treatment modalities. Since its introduction, considerable efforts have been made by clinicians and researchers to optimize drug efficacy and minimize side-effects for the patients. Furthermore, the pharmaceutical industry has increased investments into drug discovery programs to provide new molecules and biologic agents for clinical development and the pharmaceutical market. However, the amount of cancer drugs removed from early clinical trials has reached a disturbing low number, suggesting that preclinical development has not been successful in identifying agents that can modify the outcome of human cancer.
A standard in vitro screening of product libraries for novel anticancer agents mainly relies on cytotoxicity assays using established cancer cell lines grown as two-dimensional (2D) cultures that exhibit a rapid, uncontrolled growth phenotype. While this approach has several strengths, 2D cell cultures show important limitations as they are not capable of mimicking the complexity and heterogeneity of clinical tumors with a specific organization and architecture. Consequently, numerous signaling pathways that govern different cellular processes are lost when cells are grown in a 2D environment.
Three-dimensional (3D) growth of cancer cells is regarded as a more stringent and representative model on which to perform in vitro drug screening. For example, 3D cell cultures demonstrate cell-cell interaction, hypoxia, and differences in drug penetration. It is now commonly accepted that in vitro 3D cultures will be able to fill the gap between conventional 2D in vitro testing and animal models. To date, several types of 3D culture models have been developed. Tumor spheroids, 3D spheroidal architectures, are one of the most common and versatile scaffold-free methods for 3D cell culture. Starting from a single cell suspension, spheroids are formed either via self-assembly or forced growth as clusters.
In our lab we are currently optimizing two methods to produce in vitro tumor spheroids with the use of the random positioning machine or the hanging drop method. With these models we hope to improve the success rates of preclinical anticancer drug testing, thereby reducing its costs and accelerating the identification of new anticancer drugs which will enable us to save the lives of millions of people suffering from cancer worldwide.