56. A NOVEL APPROACH TO QUANTIFYING THE DIFFUSIVITY OF A TUMOR
Name: Han Liang Lim
Grad Year: 2016
One of the modern challenges in cancer drug development is to create drugs that target only cancer cells. However, it is also important to ensure that the compounds developed can also physically penetrate the tumor at sufficient concentrations to ensure the complete eradication of cancer cells, as an incomplete removal of the cancer can lead to adaptive drug resistance in the surviving cancer cells. As studies have shown that the primary mode of transport within a tumor is diffusion, it is important to quantify the diffusivity of a tumor, which measures the resistance to drug penetration. To this end, we have combined a bio-fabrication technique developed in our lab and microfluidics technology to create 3D tumors in vitro by encapsulating cancer cell spheroids within a gelatin based biomaterial. By introducing fluorescent compounds that diffuse into the cancer spheroid, we can track the influx of that particular compound using high resolution confocal microscopy. We are then able to use a novel yet simple method to calculate the local diffusivity of the cancer. Using this calculated value, drug developers can then backtrack and calculate the effective concentrations required to achieve the desired effect even deep within a tumor. Furthermore, we use this technique to further probe how the changes in the cancer microenvironment can affect drug penetration and the diffusivity of a cancer spheroid. To cancer cell spheroids encapsulated within biomaterials of different rigidities, we observed a clear difference in drug penetration, which suggests that mechanical changes in the microenvironment can play a big role in determining drug efficacies even in the clinic.
Industry Application Area(s)
Life Sciences/Medical Devices & Instruments