Researchers at the University of Toronto’s Faculty of Applied Science & Engineering have designed a groundbreaking microfluidic platform that enables precise control over the shapes of tumor models. This innovation, spearheaded by Professor Edmond Young, promises to reshape cancer research by offering new insights into how tumor shapes influence cancer cell behavior and aggressiveness. These findings could open up new avenues for more personalized and targeted cancer treatments.
Traditional methods for studying cancer cells in the lab often involve creating spherical, three-dimensional cell clusters called spheroids, which simulate mini tumors. While useful, these spherical models fail to capture the full complexity of tumors found in the human body, where cancerous masses often take on a variety of irregular shapes. According to Sina Kheiri, a co-lead author of the study recently published in Advanced Materials, the inability to control the shape, recovery, and precise positioning of cancer organoids has been a significant challenge. As a result, tumors-on-a-chip, a method of simulating tumors within a microfluidic device, are often difficult to analyze because they are fixed in place and can only be observed using optical microscopy.
To overcome these limitations, the University of Toronto team developed a new platform called the Recoverable-Spheroid-on-a-Chip with Unrestricted External Shape (ReSCUE). This technology allows researchers to grow cancer organoids in any shape and then recover them from the device for detailed analysis. By offering the ability to create a diverse array of tumor shapes, the ReSCUE platform addresses a critical gap in cancer research. Kheiri highlights that many aggressive tumors in real-life cases are not spherical, and limiting studies to spherical models means missing out on understanding the full spectrum of tumor behavior. In a study of 85 breast cancer patients, for example, only 20% of the tumors were spherical, indicating the need for more versatile models.
Kheiri’s Ph.D. research, co-supervised by Professor Edmond Young and Professor Eugenia Kumacheva from the University of Toronto’s Department of Chemistry, led to the creation of the ReSCUE platform. The development was a collaborative effort involving Dr. David Cescon, a clinical scientist and breast medical oncologist at Princess Margaret Cancer Centre. Cescon’s team provided the patient-derived breast cancer cells used to create the tumor models. These cancer cells were cultivated within EKGel, a biomimetic hydrogel developed by Kumacheva’s research group. EKGel serves as a scaffold, closely mimicking the environment of human tissue and allowing the cells to grow in patterns similar to those seen in the body.
An unexpected discovery arose when Kheiri observed how the shape of the microwells—tiny cavities used to grow the tumors—affected the development of cancer cells. While experimenting with the aspect ratio of these microwells, Kheiri noticed that elongated, rod-like wells produced distinct cellular formations compared to circular wells. In particular, cancer cells in rod-shaped wells formed strands in areas of positive curvature, where the structure curved outward. These formations were not present in spherical models derived from the same cancer-cell samples. This observation led the team to systematically investigate how different shapes, including disk, rod, and U-shaped tumors, influenced cell activity.
The findings revealed that areas of positive curvature—those that bulged outward—exhibited higher cell proliferation and activity. This suggests that cells in these convex regions may be more invasive, a characteristic that could indicate greater aggressiveness in real tumors. Understanding this relationship between tumor shape and cell behavior could help researchers predict how aggressive a tumor might be, aiding in the development of more effective treatment strategies. For instance, therapies like targeted radiation or drug delivery could be fine-tuned to target regions of the tumor that show higher activity.
The ReSCUE platform’s flexibility offers researchers the opportunity to explore how different tumor shapes respond to various anti-cancer treatments, including chemotherapy and radiotherapy. Kheiri, who is now a postdoctoral researcher at the Massachusetts Institute of Technology (MIT), continues to support the further development of the ReSCUE platform. The research team has recently submitted a U.S. patent for the technology, and future plans involve enhancing the platform to include more complex features such as simulated blood vessels. This would provide an even more realistic environment for studying tumor biology and testing potential drug treatments.
Professor Young envisions that the ReSCUE platform will help researchers create more accurate and varied models of cancer, leading to better predictive tools for treatment outcomes. The addition of vascular structures, for example, would allow scientists to simulate how tumors interact with the body’s blood supply, a key factor in cancer growth and metastasis. By controlling multiple aspects of tumor development, the platform could enable drug tests that are more representative of how treatments will perform in real clinical settings.
The research collaboration also underscores the importance of integrating engineering and biomedical sciences. The development of biomimetic materials like EKGel, alongside advances in microfluidic technology, allows researchers to manipulate tumor environments in ways that were not previously possible. This integration opens the door to new discoveries in cancer biology and provides tools that can accelerate the development of therapies tailored to individual patients.
As the field of cancer research continues to evolve, platforms like ReSCUE represent a shift towards more precise and adaptable experimental setups. Rather than relying on oversimplified models, scientists can now examine the nuanced ways in which tumor shape, environment, and cell behavior interact. This deeper understanding can lead to innovations in treatment, helping to predict which therapies will be most effective for specific cancer types and stages.
Professor Young emphasizes the long-term impact of this research, noting that by refining in vitro tumor models, scientists can better understand the biology of cancer cells, leading to improved screening for drug efficacy. The ultimate goal is to make cancer treatment more personalized, moving away from a one-size-fits-all approach to targeted therapies that account for the unique characteristics of each patient’s cancer. With continued development, the ReSCUE platform could become a vital tool in the fight against cancer, facilitating research that informs clinical practices and improves patient outcomes.
Source: University of Toronto