Cancer research on chip

Cancer research on chip

It is expected that within a few years, cancer is the main cause of deaths, exceeding coronary heart disease. The incidence and prevalence numbers of cancer are still increasing. In 2015, the Netherlands will have around 700.000 cancer patients, of which a fourth breast cancer patients. Hence, it is extremely important to stimulate cancer research to analyse how cancer originates and develops. Better understanding will improve cancer treatment. In general, this research project focuses on the development of Lab-on-a-Chip (LOC) devices to improve the current breast cancer therapy regime.

This research project consists at the moment of two parts. One is the development of a LOC device to perform ex vivo drug screening experiments. Nowadays, breast cancer patients are treated according to the tumour’s location and histological features. However, it is not ensured that the prescribed drug will tackle the breast cancer, as due to genetic variation every patient has an individual response to therapy. This LOC device enables us to, before starting therapy, select ‘the right drug in the right dose for the right person’, or in other words provide personalized medicine. For this, the LOC device will consist of a dose-gradient generator followed by multiple culture chambers to analyse the effect of various (concentrations of) drugs simultaneously (Figure 1).

Figure 1. Schematic representation of the LOC device for high-throughput drug screening (yellow = electrodes; various shades of green = various concentrations drug; grey = no drug = control).

Impedance measurements will select the best working drug, i.e. the drug which is best in inducing apoptosis (programmed cell death) in tumour cells. Besides for clinical studies, this LOC device can be used for fundamental research. What are the differences between tumour cells and healthy cells, and what are the determining factors for a tumour cell to metastasize or not. This LOC device can give new insights in tumour development and provide valuable tools to develop new drugs for cancer therapy to specifically attack tumour cells (‘druggable targets’). Our initial focus is on breast cancer, however, it should be stated that this LOC device is applicable for other tumour types to fine-tune therapy and treatment of diseases at the individual level.

Recently, the hypothesis that stem cells play an important role in tumour biology has received a lot of attention. These so-called cancer stem cells have the ability for self-renewal and are pivotal in setting the heterogeneous character of a tumour. Besides influencing the origin and growth of tumours, these cancer stem cells play an important role in developing metastasis. Currently, breast cancer therapy is focused on killing the differentiated tumour cells, leaving the cancer stem cells unharmed (Figure 2). These survived cancer stem cells can form a new tumour (recurrence of disease) and metastasize to other parts in the body. Hence, specific targeting of these cancer stem cells will improve the disease-free-survival of cancer patients tremendously (Figure 2). The research on cancer stem cells is the second part of this project. Lab-on-a-Chip devices will be developed to analyse cancer stem cells in detail. A μ-flow cytometer in the clinic (point-of-care) can identify, isolate and characterize the cancer stem cells in a breast tumour biopsy. These cancer stem cells can then be transferred to another chip device (comparable to the device described in figure 1) for culturing and drug-screening experiments. These drug-screening experiments can analyse which drug can specifically target the cancer stem cell. Overall, the outcome of these experiments can provide the physician with extra information in setting the best therapy regime possible to increase the disease-free survival and with this the quality of life for cancer patients.

Figure 2. Specific targeting of cancer stem cells.

This research project is performed in close cooperation with Medisch Spectrum Twente, Hospital Group, Enschede.

Interested?

If you are interested and for instance would like to do your Master of Bachelor assignment at this project, please contact me via the email address below.

 

Contact Information

Floor Wolbers

MESA+ Institute for Nanotechnology

University of Twente

P.O. Box 217

7500 AE Enschede

The Netherlands

( +31 (0)53 489 3944
7 +31 (0)53 489 3595
* f.wolbers@ewi.utwente.nl