A new study spearheaded by researchers from Queen Mary University of London has made significant strides in the fight against pancreatic cancer. Through investigations conducted on mice, the team has identified a particular type of cell that promotes the spread of pancreatic cancer and has detected a vulnerability within these cells that can potentially be targeted with existing medications. This offers a promising new approach for treating pancreatic cancer.
Amoeboid Cells and Pancreatic Cancer
The research, published in Science Advances and funded by Barts Charity and Cancer Research UK, found that many patients’ pancreatic cancer contains cells called amoeboid cells. These are aggressive, invasive, and fast-moving cells that weaken the immune system. These cells have previously been identified in other cancers, such as melanoma, breast, liver, and prostate cancer, and have been linked with poor survival rates. This is the first time that they have been found in pancreatic cancer.
Crucially, the new study discovered amoeboid cells in pancreatic cancer produce high levels of a molecule called CD73, which drives their ability to spread and weaken the immune system. When blocking this molecule, the researchers reduced the spread of cancer to the liver and decreased the number of immune cells that supported the tumor.
Potential Treatment Strategies
The research looked at mice given anti-CD73 treatment over the short term (3 weeks) and long term where clinical endpoints were met (when an outcome that represents direct clinical benefit was achieved, such as survival, decreased pain, or the absence of disease). In the long-term group, anti-CD73 treatment reduced the incidence of cancerous tumors that spread to the liver from 66.6 percent to 36.4 percent.
While further tests would be needed involving humans to confirm the conclusions, the study suggests that blocking CD73 could be a promising approach for treating pancreatic cancer and its spread, especially considering that drugs blocking CD73 have already been developed and are being tested in clinical trials for various types of cancer.
The amoeboid cells were present in both late and early-stage pancreatic cancer. This opens up a new possible avenue of treatment in blocking CD73 early in the disease and reducing the aggressive nature of these cells and the damage they cause in the body.
Professor Victoria Sanz-Moreno, Professor of Cancer Cell Biology at Queen Mary University of London, said:
“While the results would need to be replicated in humans, they are very promising in highlighting a potential way of treating the spread of one of the most aggressive and poorly survived cancers.
“More than 10,000 people are diagnosed with pancreatic cancer in the UK every year, so finding a way to improve its extremely low survival rate even by a little could save many years of human life.
“Pancreatic cancer remains one of the deadliest cancers and current treatments are not working well. To improve these, we urgently need to understand the disease better.”
Victoria King, Director of Funding and Impact at Barts Charity said:
“The ability of cancer cells to spread to other parts of the body is one of the greatest clinical challenges to treating cancer. Our investment in cancer research at Queen Mary has helped to attract world-leading researchers to East London who are making scientific breakthroughs that could transform the lives of people with cancer. We are excited to see the insights presented in this study, which suggest a promising new approach for halting the spread of pancreatic cancer.”
Dr Claire Bromley, Senior Research Information Manager at Cancer Research UK, said:
“Thanks to research, over one million lives have been saved from cancer since the 1980s, but improvements haven’t been equal across all cancer types. Pancreatic cancer remains hard to treat and survival hasn’t improved in the past 50 years.
“Research like this is vital to innovate new ways to treat pancreatic cancer, which is the fifth most common cause of cancer in the UK. The team’s discoveries offer a promising new route for drugs of the future. However, more research is needed before these findings can move from the laboratory bench to the bedside.”
Conclusion and Future Directions
Despite advances made in early diagnosis and treatment, the survival rate of pancreatic cancer remains extremely low. Only around 7 percent of people survive five years after their diagnosis, and current therapies, which may include surgery, chemotherapy, or radiotherapy, do not work well for most patients.
Like all cancers, early diagnosis is key to improving survival rates. For pancreatic cancer, around half of all patients are diagnosed when the disease has already spread, which is one of the reasons for poor survival rates.
The researchers plan to expand their research to other cancers and see if they uncover the same link between amoeboid cells and CD73. A key focus will be breast cancer, which is the most common type of cancer in the UK and the second most common cause of cancer death in women.
Reference: “CD73 controls Myosin II–driven invasion, metastasis, and immunosuppression in amoeboid pancreatic cancer cells” by Remi Samain, Oscar Maiques, Joanne Monger, Hoyin Lam, Juliana Candido, Samantha George, Nicola Ferrari, Leonie KohIhammer, Sophia Lunetto, Adrian Varela, Jose L. Orgaz, Felip Vilardell, Jorge Juan Olsina, Xavier Matias-Guiu, Debashis Sarker, Adrian Biddle, Frances R. Balkwill, Jim Eyles, Robert W. Wilkinson, Hemant M. Kocher, Fernando Calvo, Claire M. Wells and Victoria Sanz-Moreno, 18 October 2023, Science Advances.
DOI: 10.1126/sciadv.adi0244
The research funders include Barts Charity, Cancer Research UK, and the National Institute for Health and Care Research (NIHR) Biomedical Research Centre based at Guy’s and St Thomas’ NHS Foundation Trust and King’s College London. No NIHR BRC funds were used for animal studies.