Researchers establish organoid culture models from prostate tumor biopsies

Scientists from the Urological Research Laboratory of the Department of BioMedical Research (DBMR) at the University of Bern and the Urological Department of Inselspital Bern have established organoid culture models from prostate tumor biopsies. These are small clusters of cells that can be used to test the effectiveness of various drugs. This can be used to test which treatment is most likely to benefit individual patients.

In the EU alone, 78,800 men died of prostate cancer last year. While tumors discovered early can often be completely removed by surgery and radiation therapy, the chances of successful treatment decrease if the cancer continues to metastasize. At present, doctors cannot predict the drug response or resistance to therapy in patients.

Three-dimensional structures

The team around PD Dr. Marianna Kruithof-de Julio from the Urological Research Laboratory of the Department of BioMedical Research (DBMR) at the University of Bern and Inselspital Bern has developed a new strategy for generating prostate cancer organoids that can help to assess the response to therapy, will be her Work published in the latest edition of Nature Communications. Dr. Sofia Karkampouna and Federico La Manna, the two lead authors of the paper, spent over a year and a half optimizing and efficiently designing the protocol for generating patient-derived organoids and their detailed characterization. In addition, in collaboration with NEXUS Personalized Health Technologies, they meticulously developed a medium-throughput screen for drug testing.

The PD Dr. Researchers led by Kruithof-de Julio have shown that patient-derived organoids retain relevant traits of the prostate cancer from which they originate: not only are they characterized by the same genetic mutations, but also exhibit similar gene activity patterns.

Pioneer in personalized medicine

PD Dr. Kruithof-de Julio and her team first developed a novel, early-stage, patient-derived xenograft that cannot be treated, and then tested 74 different drugs on organoids from this and other experimental tumor models. Thirteen compounds were identified that impaired prostate cancer cell viability.

The researchers then tested the effectiveness of these compounds on organoids from five prostate cancer patients – two with early-stage tumors and three with advanced metastatic tumors. Interestingly, among the hits approved to date for the treatment of leukemia, ponatinib was shown to be particularly effective in reducing organoid viability and tumor growth in vivo.

For PD Dr. Kruithof-de Julio, however, the importance of these results lies not only in the repurposing of medicines, but above all in promoting an approach that the medical community can take.

Our results pave the way for personalized medicine. In our study we only analyzed data from five patients retrospectively. However, we have clearly shown that the method is basically feasible. Organoid growth and drug testing can be done in two weeks, a time frame that is consistent with clinical decision-making. In cooperation with the Urological Department of Inselspital under the direction of Prof. Thalmann, we have already been able to prove this in several cases. “

Dr. Marianna Kruithof-de Julio, Research Laboratory for Urology, Department for BioMedical Research (DBMR), University of Bern and Inselspital Bern

“In my clinical work, I am regularly confronted with tumors that do not respond to the therapy or for which we do not know which therapy to use,” says Thalmann. “This is a further step towards individualized medicine, where we can possibly tailor treatment to the tumor as the disease progresses and better understand its biology.” With this approach, the researchers hope to be able to treat patients more efficiently with fewer side effects and lower costs.

Source:

Journal reference:

Karkampouna, S. et al. (2021) Patient-derived xenografts and organoids model therapy response in prostate cancer. Nature communication. doi.org/10.1038/s41467-021-21300-6.

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