IISc Breakthrough in Cancer Research

Introduction to Cancer Research

Cancer is a complex and multifaceted disease that affects millions of people worldwide. Despite significant advances in cancer treatment, there is still much to be learned about the disease and how to effectively combat it. Researchers at the Indian Institute of Science (IISc) have made a breakthrough in cancer research by developing a 3D-printed device that can help scientists understand how cancer drugs penetrate tumours.

The device, which was developed by researchers from IISc's Department of Chemical Engineering, recreates the nutrient- and oxygen-deprived conditions found inside tumours. This allows researchers to examine how cancer cells respond to drugs at different depths, which is crucial for understanding why cancer drugs are often less effective in deeper regions of solid tumours.

The Challenge of Reproducing Tumour Conditions

One of the major challenges in cancer research is reproducing the complex microenvironment of solid tumours in laboratory conditions. In solid tumours, blood vessels are often poorly developed and unevenly distributed, which means that cells closer to blood vessels receive more oxygen and nutrients, while those farther away experience shortages. These differences can influence how cancer cells grow and respond to treatment.

Conventional laboratory methods that grow cancer cells in flat, two-dimensional layers do not adequately reproduce these conditions. To overcome this limitation, researchers have developed the 'Cells-in-Gel-in-Paper' (CiGiP) model, in which cancer cells embedded in a gel are grown on stacked paper layers. However, existing versions of this technique rely on wax-printed or hydrophobic barriers to contain the cell culture within each paper layer, which can be limiting.

The IISc Solution

The IISc team has replaced this requirement with a simple press-fit enclosure made using fused deposition modelling (FDM) 3D printers. Designed by Ankit Kumar, a PhD student in the laboratory of Bhushan J Toley, the device holds eight circular paper discs together through gentle, uniform pressure, preventing nutrients and drugs from leaking around their edges. Culture medium is supplied through an inlet at the top.

The researchers tested the platform using MDA-MB-231 breast cancer cells embedded in Matrigel. After 72 hours, they found that the number of live cells progressively decreased from the topmost to the bottommost layer, while dead cells increased. Expression of HIF-1alpha, a gene associated with low-oxygen conditions, also rose towards the deeper layers, confirming that the model recreated a hypoxic tumour-like environment.

Testing the Device

The team then examined how the chemotherapy drug doxorubicin penetrated the tissue. Drug uptake declined progressively across the eight layers, indicating that deeper regions received less of the drug. Longer treatment periods partially overcame these diffusion limitations.

The researchers also tested doxorubicin and paclitaxel, individually and in combination. Using a statistical method called the Bliss synergy score, they found that the two drugs had an antagonistic interaction across all eight layers when administered together. This means their combined effect was lower than what would be expected if the drugs acted independently.

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• The device was designed by Ankit Kumar, a PhD student in the laboratory of Bhushan J Toley.
• The device holds eight circular paper discs together through gentle, uniform pressure.
• Culture medium is supplied through an inlet at the top.
• The researchers tested the platform using MDA-MB-231 breast cancer cells embedded in Matrigel.

Implications for Cancer Research in India

The IISc team's breakthrough in cancer research has significant implications for cancer research in India. Cancer is a major health concern in India, with over 1.4 million new cases diagnosed every year. The development of a low-cost, 3D-printed device to study cancer drug penetration in tumours could lead to more effective treatments and improved patient outcomes.

Expert Perspective

According to Bhushan J Toley, the lead researcher on the project, the device has the potential to revolutionize the field of cancer research. 'The ability to study how cancer drugs penetrate tumours in a controlled laboratory setting could lead to the development of more effective treatments and improved patient outcomes,' he said.

What to Watch Next

As the IISc team continues to refine their device and explore its applications, there are several things to watch next. The team plans to test the device with other types of cancer cells and to explore its use in combination with other cancer treatments. Additionally, the team is working to make the device more widely available to researchers and clinicians, which could lead to a greater understanding of cancer and the development of more effective treatments.

Conclusion

The IISc team's breakthrough in cancer research is a significant step forward in our understanding of cancer and how to effectively treat it. The 3D-printed device provides a low-cost and accessible way to study how cancer drugs penetrate tumours, which could lead to the development of more effective treatments. As the team continues to refine their device and explore its applications, it is clear that this technology has the potential to make a significant impact on the field of cancer research.