About This Project

Most cancer-related deaths are caused by metastasis, the spread of cancer cells to distant tissues. This process depends on signalling proteins activated by the enzyme GGPPS (geranylgeranyl pyrophosphate synthase). Despite this, metastasis remains largely overlooked in drug discovery. We hypothesize that inhibiting GGPPS will preferentially disrupt metastasis-associated signalling, revealing GGPPS as an underexplored anti-metastatic drug target.

Ask the Scientists

What is the context of this research?

Although GGPPS plays a central role in cancer biology, it has been difficult to target in drug discovery. The human enzyme is large, forms complex assemblies, and has been challenging to study using traditional screening methods. As a result, very few drug programs have been able to explore GGPPS as a therapeutic target, leaving a major gap in the development of treatments that intervene in this pathway. Currently, no clinically relevant inhibitors of human GGPPS exist.

Our lab recently overcame these limitations by engineering a stable, research-friendly version of human GGPPS. This new form of the enzyme allows us to screen molecules more accurately and to grow crystals that reveal how potential inhibitors bind. With this improved version in hand, we now have a rare opportunity to explore a cancer-relevant target that has remained out of reach for most research groups.

What is the significance of this project?

If we can identify molecules that disrupt GGPPS, we open the door to an entirely new strategy for slowing or stopping the spread of cancers. Most treatments and research focus on tumour growth, but far fewer address the signals that allow cancer cells to move, invade, and become deadly. By finding the first drug-like compounds that act on GGPPS, this project could reveal a target that has been largely overlooked in cancer research. Given that an estimated 90% of cancer deaths are due to its spread, this is a large gap in research.

Beyond discovering individual compounds, this work also creates a foundation for future drug development. Any promising inhibitors we find can guide medicinal chemistry, cell-based studies, and eventually more advanced therapeutic approaches. All results will be shared openly, helping other researchers build on our findings and accelerating progress in an area that urgently needs new ideas.

What are the goals of the project?

Once the project is funded, we will begin by using computer-based molecular docking to screen large, curated collections of existing chemical compounds for their ability to bind the cancer-relevant enzyme GGPPS. These compounds are drawn from established databases of approved, experimental, and cancer-associated molecules and are all commercially available for purchase. This computational step allows us to efficiently narrow thousands of possible compounds down to a small set of promising candidates. We will then order approximately 20–30 of these compounds and test whether they bind to GGPPS and inhibit its activity using established biochemical assays. Compounds that show clear inhibition at low micromolar concentrations or better will be prioritized, and the strongest candidate will be examined further to understand how it interacts with GGPPS at the molecular level. All results will be shared openly so others can build on these findings.