Predicting which treatment is best for a bladder cancer patient, without burdening someone with surgery… Researchers at UMC Utrecht do this with the help of so-called ‘urinoids’: mini-bladder cancer tumors, which are grown from urine in the lab. The only substance the researchers need for this: urine from the patient.
Worldwide, bladder cancer is in the top 10 of most common cancer types. More men than women are affected, but the number of women with the disease has increased significantly in recent years. An important risk factor is smoking. The disease is generally detected late and is therefore difficult to treat.
“Usually people with muscle-invasive bladder cancer first receive chemotherapy and then surgery. But in three out of four patients, chemotherapy does not have an optimal effect. We find out through trial and error,” says Richard Meijer, oncological urologist and associate professor at UMC Utrecht. “So, everyone gets the same treatment and we conclude afterwards whether someone has benefited from it. Of course, this is not an ideal set-up because they all get side effects and are exposed to risks, while only the minority clearly benefits from it.”
That is why Richard and his colleagues have been looking for an ‘environment’ in which they can better investigate the effect of treatments, without exposing bladder cancer patients to additional risks or procedures. They have now found that environment in urinoids.
“Strangely enough, no one had ever thought of growing bladder cancer from urine. But here in Utrecht, we have done precisely that, and we are the first in the world to do so.”
Mini-organs to the rescue
Urinoids are derived from organoids. These are mini-organs or mini-tumors grown in a laboratory. Tissue from an organ or tumor is taken from patients and researchers grow three-dimensional miniature look-alikes from it in the lab. These have the same genetic properties as the original tissue.
Organoids were invented in 2009 by Hans Clevers (then Professor of Molecular Genetics at UMC Utrecht) and his research group at the Hubrecht Institute. The ‘father of the organoid’ and his team grew a mini-intestinal tract from the intestinal cells of a mouse. This first ‘organ-in-a-dish’ marked a global revolution in personalized medicine.
Organoids help to treat a patient in a tailor-made way instead of giving everyone the same standard treatment. With the help of these three-dimensional cultures, treatments can be developed, improved and tried, but they also help to better understand (complicated) diseases.
Bladder tumor in a dish
Richard and his team contacted the Hubrecht Institute in 2016, in their quest to better ‘personalize’ treatments for bladder cancer. Together with the research institute, they then started a bladder cancer project.
“We have taken tumor tissue from more than 50 patients and built a ‘living biobank’. We made small cultures of the tissue and compared them with the original tumor,” Richard explains.
The properties of these bladder cancer organoids turned out to correspond very precisely with those of the original tumors. “We also investigated whether those cultures could be used in drug research, for example to look at the effect of chemo. And that turned out to be positive as well.”
Bladder cancer collection
In 2020, UMC Utrecht, together with IKNL and a number of other academic hospitals, set up the Prospective Bladder Cancer Infrastructure (ProBCI)). In it, biomaterial, medical information and other data from people with bladder cancer are collected to conduct scientific research. Goal: to improve the treatment, prognosis and quality of life of (future) bladder cancer patients. 23 hospitals, the patient association ‘Leven met Blaas- of Nierkanker’ (‘Living with bladder or kidney cancer’) and the Dutch Uro-Oncology Studygroup (DUOS) are working together within the ProBCI. The data of more than 1,300 patients have now been included.
Urine instead of surgery
However, something kept gnawing at the researchers: organoids are grown with tissue, and it always takes surgery to get hold of that tissue. And that is drastic for a patient, who is not in top shape due to the cancer and treatments.
Two years ago, Richard and his colleagues therefore came up with the idea of using urine instead of tissue. The big advantage: no surgery is needed, someone only has to pee in a jar.
Richard: “One of the characteristics of bladder cancer is that the tumor cells are excreted in the urine. They float around in the urine, as it were. Worldwide, this is already used to see if cancer is present, but strangely enough, no one had ever thought of making tumor cultures out of it. Here, in Utrecht we have done precisely that, and we are the first in the world to do so.”
Successful project
The researchers have now compared these urinoids with the original bladder tumors to check whether their characteristics are indeed the same, as was the case with the organoids before. Because only then urinoids are suitable as a research environment.
“We looked at the genetic characteristics and the histology (tissue properties) of the tumors and the urinoids. And they both turned out to be a good match,” says Richard. In addition, it was also possible to test the sensitivity to chemotherapy with the urinoids.”
After this first successful research project, the researchers have now started a series of follow-up projects with urinoids. They do this within the Laboratory for Translational Oncology (LTO) of the UMC Utrecht. Within this, the clinic (patient care) and lab work closely together: doctors, nurses and researchers join forces to find and apply the best treatments for patients with cancer more quickly.
In the laboratory, which is led by Onno Kranenburg (Professor of Surgical and Translational Tumor Biology), a special bladder cancer research group has been set up. Within this, Richard works together with medical oncologist Britt Suelmann, researcher Alba Zuidema and PhD student Bas Viergever, among others.
Utrecht Cancer: uniting expertise and innovation
At the Utrecht Science Park, various institutions are committed to better understand and treat cancer. They have united within Utrecht Cancer.
The more than 1,200 researchers from UMC Utrecht, the faculties of Veterinary Medicine and Science of Utrecht University, Hubrecht Institute and the Princess Máxima Center share their knowledge, innovation and experience to accelerate the treatment, quality of life and survival rates of adults, children and animals with cancer. Utrecht Cancer also encourages collaboration with other (public or private) parties.
Peeing in the jar in the meantime
Bladder cancer patients who are treated with chemo- and/or immunotherapy at UMC Utrecht are asked if they want to participate in the study, and then urine cultures are made at different times.
“We also ask patients to urinate in a jar during treatment to make a new urinoid. This allows us to check whether the tumor has changed due to the therapy,” Richard explains.
“For example, chemotherapy can cause the tumor to develop other characteristics that make it insensitive or more sensitive to certain treatments. We will recognize that sooner, so that we can adjust the treatment more quickly in the future.”
By making these interim repeat cultures, the researchers also aim to switch more quickly between various types of treatments. Richard: “At what point do we give chemo, and when do we start immunotherapy? Do we give chemo first, or do we operate first? Is there still an advantage to be gained after two courses of chemo? We would like to further develop this approach in the coming years. By treating patients in a more customized and personal way with the help of urinoids, we will better understand bladder cancer, reduce side effects and improve the results of treatments faster.”
Want to know more?
Richard Meijer tells more about urinoids in this video (starts at 3:20).
Richard and his colleagues have published a scientific article on urinoids in the British Journal of Cancer.
What symptoms are associated with bladder cancer? What treatments are available? On our website, you will find extensive information about bladder cancer (in Dutch).
Further research on urinoids requires funding. On the website of Vrienden van UMC & Wilhelmina Kinderziekenhuis, you will find more information about how you can help us with this research (in Dutch).
