An team of researchers from Israel and Germany has uncovered a promising new avenue in treating colorectal cancer, the world’s third leading cause of cancer-related deaths. By analysing patient-specific genetic data, scientists identified a protein system that could predict chemotherapy resistance and open the door to more tailored, effective treatments.
The study was jointly led by Prof. Michal Linial, Prof. Or Kakhlon and Keren Zohar at the Hebrew University of Jerusalem together with Prof. Dr. Ulf Kahlert and Dr. Marco Strecker at the Universitätsmedizin der Otto-von-Guericke-Universität Magdeburg. Additional contributions came from the Hadassah-Hebrew University Medical Center , the National Center for Tumor Diseases Dresden (NCT/UCC) and the University Hospital Dresden.
In the current study, the researchers analysed tissue samples from 32 patients with colorectal cancer. The focus was particularly on the protein xCT, which controls central metabolic processes in cancer cells and is important for their growth. The results showed that tumors with high xCT activity respond significantly better to certain chemotherapies. This means that xCT could serve as a biomarker in the future to assess the chances of success of certain therapies before treatment begins.
In order to select the most appropriate therapy, the research team relied on organoids: tiny tumors grown in the laboratory that precisely replicate the original tissue. They allow drugs to be tested directly on tumor and normal tissue without placing unnecessary strain on patients.
“Our study shows the power of integrating patient-specific data with functional models,” says Prof. Linial. “This approach doesn’t just identify what makes each patient’s tumor unique, it shows us where the cancer is most vulnerable.”
“Our results suggest that we can predict more accurately which therapy will work best for which tumor,” explains Prof. Dr. Ulf Kahlert, head of the study and professor of molecular and experimental surgery at the Department of General, Visceral, Vascular, and Transplant Surgery at the Medical Faculty of Otto von Guericke University Magdeburg. “Those with high xCT levels in their tumors could potentially benefit from targeted combination therapy. Individuals with low levels could avoid unnecessary side effects.”
The research paper titled “Patient-specific pharmacogenomics demonstrates xCT as predictive therapeutic target in colon cancer with possible implications in tumor connectivity” has been published in Molecular Oncology and can be accessed at https://febs.onlinelibrary.wiley.com/doi/10.1002/1878-0261.70129.