Cancer is still a leading cause of death globally. Consequently, research into development of new therapies is widespread and there is a great demand for better systems to test their effectiveness.
A research group in Korea aims to contribute to the improvement of testing platforms with a system that allows them to model an important structure in cancer, the tumour microenvironment (TME). The TME surrounds a developing tumour and plays a key role in cancer progression and invasion. Understanding the function of the TME is critical to getting a better understanding of how to develop more effective anticancer therapies.
This is a significant step forward in cancer research because, while progress in developing treatments has been made in recent decades, there are still many cancers that lack an effective medical therapy.
One major reason for this is the difficulty in developing effective anticancer drugs. Research institutes across the globe continue to design and test potential new drugs on a huge scale.
However, the success rate for FDA approval of anticancer drugs is extremely low. This means, for every 100 new drugs that show promise, scientists are lucky if just 1 of them makes it to the clinic.
There is potential, however, to increase this success rate by improving the platforms scientists use for early testing of anticancer drugs. Generating more reliable early data would allow researchers to better identify the most promising candidates for clinical trials.
Modelling The Tumour Microenvironment
The TME surrounds a developing tumour and plays a key role in cancer progression and invasion. Understanding the function of the TME is critical to getting a better understanding of how to develop more effective anticancer therapies.
The group focussed on cancers of the liver and sought to mimic the TME in which they progress. A model was designed around a three dimensional mesh of nanofibres which resembles the structural component of a TME, namely the extracellular matrix.
[caption id=“attachment_94375” align=“aligncenter” width=“680”] Credit: Binh Duong Le, et al. CC-BY[/caption]
In addition to this, the researchers incorporated two cell types that are primarily involved in tumour progression. Human hepatocellular carcinoma (liver cancer) cells were grown on the nanofibres along with fibroblasts (non-cancerous cells that are thought to influence tumour progression).
Combination of all these components produces a very rigid model of the TME that has a lot of potential in the field of cancer research. The most exciting application is in the initial evaluation of anticancer drugs.
Improved Anticancer Drug Screening
The researchers were able to grow cells in three different conditions to represent various stages of cancer progression. In each condition, cells displayed changes in behaviour showing the potential to test anticancer drugs at different points of tumour development.
However, the most interesting result came when the researchers tested a clinically approved anticancer drug (methotrexate) on the cells in their model. The cancerous cells showed evidence of resistance to drug treatment, a common problem in anticancer therapies.
[caption id=“attachment_94376” align=“aligncenter” width=“680”] Images of E-cadherin expression at cell-cell junctions of Hep G2 cells .
Credit: Binh Duong Le, et a;. CC-BY[/caption]
What is promising, however, is the fact that the researchers were able to probe each aspect of their model to gain a better understanding of why the cancer cells showed drug resistance. Data like this can then be fed into improving the drug to make it more effective.
Technologies such as this are arguably one of our best avenues for improving efficacy of cancer treatments. A lot of progress is hindered by our inability to gain the best possible understanding of how potential new drugs act in the environment of a developing cancer.
If we can improve the selection of candidates for clinical trials, it is hoped that we will see the success rate of new drugs dramatically increase. Developments such as this provide promise that we are moving in the right direction.
Le, B., Kang, D., Yun, S., Jeong, Y., Kwak, J.-Y., Yoon, S. & Jin, S. Three-Dimensional Hepatocellular Carcinoma/Fibroblast Model on a Nanofibrous Membrane Mimics Tumor Cell Phenotypic Changes and Anticancer Drug Resistance Nanomaterials, 2018, 8, 64, DOI: 10.3390/nano8020064
Author: Dr Sam Moxon; Biomaterials Research Associate at the University of Manchester
Top Image: Structural morphology of cancer cells and fibroblasts or cancer cells alone on the nanofibrous membrane after seven days of culture. Credit: Binh Duong Le, et al. CC-BY