Organoids derived from people with pancreatic cancer can help to determine whether potential drugs will be effective. Credit: ATCC
Christian Pilarsky vividly remembers the moment, in 2022, when he realized that his technique for modelling pancreatic cancer had finally worked. A molecular biologist at the University Hospital Erlangen in Germany, Pilarsky had been struggling for three years to perfect the method, which involves growing miniature 3D replicas of pancreatic tumours derived from a person’s cells. “Trying this and trying that” and correcting errors along the way, he and his colleagues could eventually grow organoids from six out of every ten people they took cells from. The results produced “a kind of happiness only experimental scientists understand,” Pilarsky says. “It’s nearly as good as the moment after a child is born.”
Robust models of pancreatic cancer, such as Pilarsky’s organoids, are increasingly a key component of developing treatments for pancreatic cancer, which has one of the lowest survival rates of all major cancers. Models are used in research to improve treatments and detect the disease before it spreads beyond the pancreas. They are also used to investigate fundamental questions about the cancer’s aggressive nature and its resistance to therapies. Ultimately, they “are a way of understanding the biology of a tumour without doing clinical research on patients”, says Ben Stanger, a gastroenterologist at the University of Pennsylvania in Philadelphia. This allows researchers to capture the diversity of pancreatic cancer much more quickly and cheaply than they ever could with older techniques.
Nature Outlook: Pancreatic cancer
Organoids are only one of a growing number of modelling tools. Other experimental systems include specialized animal models that have been engineered to develop pancreatic cancer, or that are injected with human tumour cells. Researchers are also turning to computer models and artificial intelligence to discern patterns in patient records that might help to predict which individuals will go on to develop the disease.
These efforts have the support of governments on both sides of the Atlantic. In Europe, an initiative across nine countries called Pancreatic Cancer Organoids Research, known as PRECODE, has established 13 centres of excellence for organoid research. Since 2020, this has led to at least 80 new pancreatic cancer organoids. In September, the US National Institutes of Health (NIH) announced plans for a centre dedicated to organoid-based modelling, following an earlier US announcement that called for a move away from animal models.
“The disease is tough but not unbeatable, and the models are going to help us win,” says David Tuveson, a cancer biologist at Cold Spring Harbor Laboratory in New York. “I’m the most excited I’ve ever been about our field.”
Microtumours and mini-organs
Tuveson has had a front-row view of progress in the field since 2015, when he and his colleagues developed the first pancreatic cancer organoids1. This breakthrough began to address issues that scientists working with pancreatic cancer cells in a dish had been facing for decades: the cells did not represent the complex, 3D nature of how tumours function in a body, says Carolina Lucchesi, head of microphysiological systems at the American Type Culture Collection (ATCC) in Manassas, Virginia, a non-profit organization that provides cells and microorganisms for research.
Organoids got around these limitations. Unlike 2D cell lines, their 3D structure preserved the architecture, heterogeneity and drug responses of an individual’s tumour.
... continue reading