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The Humane Research Trust is funding a research project to help us understand why tumours become drug-resistant and find ways to prevent this from happening. Researchers at the University of Sheffield are using lab-grown tumours to shed light on the mechanisms that underly drug-resistant tumours. They are also using this model to test novel treatments.
Non-small-cell lung cancer (NSCLC) accounts for 84% of lung cancers, making it the second most common cancer and the leading cause of cancer death. Most patients with this type of lung cancer will develop drug-resistant tumours after one year. Unfortunately, less than 15% of NSCLC patients survive 5 years.
A combination of chemotherapy and radiotherapy is the standard treatment for this type of lung cancer. These treatments work by damaging the DNA, an essential blueprint containing all the instructions required for organisms to survive and grow. This particularly impacts cancer cells, which have a reduced capacity to repair their DNA. However, in many cases, NSCLC cells are becoming resistant to existing treatments, negatively affecting patient outcomes.
Repeated exposure to chemotherapy and radiation treatment can cause drug-resistant tumours to develop. Cancer cells can build up resistance to DNA damage, and these cells can continue to multiply. Over time, the treatment becomes less effective, resulting in many patients dying prematurely.
Scientists are currently undertaking research to understand the exact processes that cause drug resistant cancer cells to multiply. Cells check their DNA for damage at essential points in their lifecycle, these are called checkpoints. If the cell detects damage, it delays the cellular schedule, allowing repair machinery to correct the damage. There are established checkpoints before and after DNA replication, which ensures that errors are not passed on to subsequent generations.
Researchers at the University of Sheffield recently discovered a previously unidentified checkpoint, which occurs at the point of mitosis, or cell division. This checkpoint uses different repair machinery to the other checkpoints, which could explain why resistance occurs. The scientists also identified a protein that is required for this checkpoint. When present in high levels, this protein seems to lead to shorter survival in NSCLC.
The Humane Research Trust is funding a research project at the University of Sheffield to explore these findings. Dr Ruth Thompson and her researchers are investigating the role of this key protein and testing a novel drug that inhibits it. They hope that supplementing cancer treatment with this drug will make the treatment more effective.
The researchers are going beyond standard cell culture techniques, using a three-dimensional cell culture model known as a tumour spheroid. This method involves culturing cells in a round bottomed well, suspended in liquid. The seeded cells aggregate, then grow outwards, forming cellular tumour organoids.
“Standard cell culture approaches are often acceptable for early studies, but are not an accurate representation of how tumours grow in the body. Hence, scientists typically use animals in cancer research,” said Dr Thompson. “We only use human cells for our research as we believe that human cell models much more accurately depict the drug response of human tumours.”
