Better understanding of chemokine receptors paves the way to better cancer treatments
Pharmacologist Kylie Pan investigated chemokine receptors that are increased in various types of cancer. Her research leads to more knowledge that can help develop new treatments for cancer.
Our body uses signals to control how cells should behave. An important group of proteins on cells that receive these signals are the G-protein-coupled receptors (GPCRs). Chemokine receptors are part of these GPCRs and play a crucial role in guiding immune cells to the right place in the body.
Better therapies
Pan's research focuses on two specific chemokine receptors, CXCR4 and ACKR3, which both respond to the same signaling molecule, CXCL12. Because these receptors are increased in various types of cancer, they are interesting targets for new drugs. The aim of this research is to develop better therapies by better understanding the biology of these two receptors.
The research focused on three important questions:
1. How does the drug TG-0054 (Burixafor) block CXCR4? The researchers found that CXCL12 prevents binding to the receptor and affects the function of CXCR4 in a unique way. This makes TG-0054 a useful tool for further research.
2. How can we mathematically model CXCR4 signals? Using computer models, Pan and her colleagues analyzed how CXCR4 works and why TG-0054 behaves differently from other drugs.
3. How do CXCR4 and ACKR3 affect each other? The researchers found that ACKR3 not only removes CXCL12 from the environment (as previously thought), but also affects the activity of CXCR4 in an unexpected way.
The research contributes to a better understanding of how these receptors work, which can help in the development of new cancer treatments. It also shows how powerful mathematical models can be in studying biological processes.
Mathematical models
Pan conducted her research with cells, in which we added the specific receptors, CXCR4 and ACKR3. She then used various measuring devices to determine how the cells responded when exposed to drugs. She also looked at previous research to understand how these receptors send signals inside the cell. She then wrote simple mathematical equations to explain these processes.
Pan: ‘My research has broad societal implications, especially in the area of improved cancer treatments through the development of more targeted and effective drugs. By better understanding CXCR4 and ACKR3, my findings contribute to precision medicine, which can lead to personalized therapies with fewer side effects. The use of mathematical models in my study underscores the growing role of computational tools in drug development and bridges the gap between biology and technology.’
