Researchers at the German Cancer Research Center (DKFZ), the Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM) and the biotech company Xilis have developed a method that can predict which chemotherapy will work best for advanced colorectal cancer even before therapy begins. The basis is tiny, three-dimensional tumor models – so-called MicroOrganoSpheres (MOS) – which are produced from tumor tissue of individual patients in the laboratory and automatically tested.

Primary sclerosing cholangitis (PSC) is a chronic inflammation of the bile ducts that, if left untreated, often leads to liver failure and often requires a liver transplant. The disease affects about one in 10,000 people in Germany and usually occurs between the ages of 30 and 50. A cure is currently not possible; treatment is limited to symptom relief.

The MOS technology is based on tumor cell suspensions that are broken down into tiny droplets (approx. 300 micrometers) by microfluidics and embedded in a gel matrix. These microtumors grow quickly, are highly reproducible and are optimally supplied with nutrients. In the high-throughput process, they can be treated with various chemotherapeutic agents. Modern image analysis and artificial intelligence then measure the reaction of the tumor cells.

The team tested the method on MOS from tumor samples from 21 patients with advanced colorectal cancer. In 83 percent of the cases, the response of the microtumors matched the actual clinical treatment success. If the MOS was obtained from the primary tumor (and not from metastases), the prediction accuracy was 100 percent. Patients whose MOS responded to the chemotherapy tested in the laboratory remained disease-free for longer on average. In addition, the method was able to detect intratumoral heterogeneity and identify particularly resistant cell populations.

The researchers see the MOS as a promising step towards functional, personalized cancer medicine. Compared to conventional organoids, the test is standardized, automatable and can be performed within a few days – prerequisites for possible later routine use in the clinic. René Jackstadt, head of the study at the DKFZ and HI-STEM, emphasized that the technology could contribute to more tailored and precise treatment in the long term. However, further validations in larger patient cohorts in clinical trials are required before widespread use.

The results have been published in the journal JCO Precision Oncology (DOI: 10.1200/PO-25-00501).

Editor: X-Press Journalistenbüro GbR

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