Exploring Cancer Complexity: 3D Models Offer New Insights

Phil Stevens
24th January, 2024

Exploring Cancer Complexity: 3D Models Offer New Insights

Figure 1 from study, showing how cell interactions in the tumor microenvironment shape disease progression.

Image adapted from: Rodrigues et al. / CC BY (Source)
Cancer treatment development faces a significant hurdle: accurately replicating the complex environment within a tumor when testing new drugs. Traditional methods often rely on growing cells in two-dimensional (2D) cultures, which don’t fully represent the conditions found inside the body. Animal models, while useful, have limitations in mirroring human cancer development[2]. Researchers at the University of Minho have been investigating how well three-dimensional (3D) spheroid models – essentially tiny, spherical clumps of cancer cells grown in the lab – can overcome these challenges[1]. Tumors aren’t simply masses of cells; they involve intricate interactions between the cancer cells themselves, and the surrounding tissue, known as the extracellular matrix (ECM). This ECM provides structural support but also influences how cancer cells grow, spread, and respond to treatment. The study focuses on how effectively current 3D spheroid models capture these crucial interactions that drive tumor behaviour. The core problem is that 2D cell cultures lack the necessary physical and chemical cues present in a real tumor. Cells grown on a flat plastic surface behave differently than those embedded within a 3D environment. This discrepancy contributes to a high failure rate in drug development, as drugs that show promise in 2D cultures often fail in clinical trials[3]. 3D models aim to bridge this gap by providing a more realistic setting for testing potential therapies. Spheroids are created by allowing cancer cells to grow in a way that they self-assemble into these spherical structures. This process naturally leads to differences in oxygen and nutrient levels within the spheroid, mimicking the conditions found in solid tumors where cells further from blood vessels may be deprived. These gradients influence cell behaviour and drug response. The researchers highlight that successful 3D models need to reproduce key aspects of tumor biology, including cell-to-cell communication, the interaction between cells and the ECM, and the physical forces within the tumor. They review how well current spheroid models achieve this. For example, the ECM isn’t just a passive scaffold; it actively influences cell shape, migration, and gene expression. Importantly, the study acknowledges that 3D cultures can exhibit increased resistance to anti-cancer drugs compared to 2D cultures[4]. This is due to changes in protein expression, increased activity of drug transporters (which pump drugs out of the cells), and altered drug metabolism. This finding underscores the importance of using 3D models in preclinical drug testing to better predict how drugs will perform in patients. Furthermore, the study touches upon the importance of modelling tumor invasion – the process by which cancer cells spread to other parts of the body. Advanced models, such as microfluidic chips, are being developed to recreate the complex interactions between tumor cells and the surrounding stroma (the connective tissue that supports the tumor)[5]. These models allow researchers to observe cancer cell invasion in real-time and identify factors that promote or inhibit this process. Looking ahead, the researchers suggest that future advancements in 3D spheroid models will focus on incorporating even more complexity. This includes mimicking the immune system’s response to tumors, recreating the blood vessel network that supplies tumors with nutrients, and developing models that can be personalized to individual patients. These improvements will ultimately lead to more accurate and reliable drug screening platforms, accelerating the development of new and effective cancer treatments.

MedicineHealthBiotech

References

Main Study

1) Modelling the complex nature of the tumor microenvironment: 3D tumor spheroids as an evolving tool.

Published 23rd January, 2024

https://doi.org/10.1186/s12929-024-00997-9

Related Studies

3) Three-Dimensional in Vitro Cell Culture Models in Drug Discovery and Drug Repositioning.

https://doi.org/10.3389/fphar.2018.00006

4) The relevance of using 3D cell cultures, in addition to 2D monolayer cultures, when evaluating breast cancer drug sensitivity and resistance.

https://doi.org/10.18632/oncotarget.9935

5) Breast Cancer Cell Invasion into a Three Dimensional Tumor-Stroma Microenvironment.

https://doi.org/10.1038/srep34094


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