For many years, the Fund has supported research at City St George’s, University of London in Tooting, South London, investigating how different combinations of medicines affect pancreatic cancer cells.
Pancreatic cancer remains one of the hardest cancers to treat. While survival rates for many other cancers have improved dramatically over the past 50 years, outcomes for pancreatic cancer have changed little. Early detection is difficult, and according to NHS data, most patients make three or more visits to their GP before being referred to a hospital specialist. Even once diagnosed, pancreatic tumours are often resistant to treatment and adapt quickly to new drugs.
Time is critical in pancreatic cancer. That is why our current research focuses on a simple but potentially powerful question: can a well-established family of safe, non-cancer medicines be repurposed to weaken pancreatic cancer cells?
Because these medicines are already known to be safe and inexpensive, successful results could speed up progress and make future treatments more accessible.
What We Are Doing in the Lab
We use panels of pancreatic cancer cell lines — laboratory models that mimic different tumour types — and test how they respond to treatment. By combining different experimental approaches, we can study both what happens to the cells and how the medicines work inside them.
1. Do the cells live or die?
We use dye-based and metabolic tests to count living cells and extended “regrowth” tests to see if any survivors can form new colonies. This helps us understand both immediate and long-term drug effects and provides clues about resistance.
2. What is happening inside the cells?
We measure key protein signals that control cell behaviour — including those involved in:
- The self-destruct programme (apoptosis) that removes damaged cells,
- How cells sense nutrients and recycle components under stress (autophagy and mTOR pathways),
- The shape-shifting process that allows cells to move and resist treatment (EMT), and
- The growth-control systems that decide when a cell divides or rests.
3. Where in the cell cycle do they stall?
We can see whether the medicines make cells pause at specific checkpoints, which often reveals how they slow or stop tumour growth.
4. Mapping the cancer’s weak spots
To understand which genes, make tumour cells more or less sensitive to treatment, we conducted a broad genetic screen. This large-scale test gently disrupted thousands of genes, one by one, to see which changes mattered most. It’s analogous to flicking every switch in a fuse box, one at a time, to find out which circuit controls the lights — except here, the “lights” are the cancer cells’ survival systems.
From this research, we have identified a shortlist of promising “control switches” that seem to govern drug response. We are now busy at work confirming these results and testing the “switches” to verify and independently confirm the results are valid.
What we’re seeing so far
- Strong signs of cell death: Under certain conditions, the medicines trigger cell death in cancer cells while sparing healthy cells.
- Nutrient stress: Pathways that help tumour cells manage energy and resources are disrupted.
- Reduced plasticity: Proteins linked to invasion and drug resistance shift in a direction less favourable for tumour spread.
- Multiple cancer pathways affected: The medicines appear to work through several biological routes at once — not a single “magic bullet,” but a coordinated attack on multiple lifelines.
Why our results matter
Cancer rarely has one weak spot. Tumours survive because they can reroute their internal systems when one pathway is blocked. A treatment that pressures several of these survival routes simultaneously (and that combines safely with existing drugs) stands a better chance of ongoing success.
Our early data suggest these medicines do exactly that. They act on multiple pathways at once and may work best in combination therapies, where the joint effect is greater than the sum of the parts.
Whether these drugs will have the same positive effects in patients as we see in the laboratory remains to be seen. However, our research is ongoing and each new experiment brings us closer to understanding how these medicines could be adapted for one of the toughest cancers to treat.
Previous Research
Before our current project began, our laboratory discovered that pancreatic cancer cells release tiny parcels, known as extracellular vesicles, which carry chemical messages to neighbouring cells. We found that these parcels can reduce the effectiveness of standard chemotherapy combinations — but when their release was blocked, the treatment began to work again. These results were published in the International Journal of Molecular Sciences (2022) and are available online:
Extracellular Vesicles Inhibit the Response of Pancreatic Ductal Adenocarcinoma Cells to Gemcitabine and TRAIL Treatment
