BOTCAT: Goal achieved
The Clinical Pharmacy and Pharmacotherapy Research Group in the Department of Pharmacy at LMU Munich, led by Prof. Dr. Oliver Scherf-Clavel, has successfully completed the pilot study BOTCAT: Biomarkers to Guide Oral Targeted Cancer Therapies, which was funded by the FFQM. We congratulate Mr. Jonathan Sirois, who conducted the study as part of his dissertation, and the entire research team.
The research group is participating in the multicenter, non-interventional ON-TARGET study on therapeutic drug monitoring (TDM) in patients with renal cell carcinoma (RCC). The BOTCAT proteomics pilot study aimed to identify potential protein biomarkers for adverse drug reactions (ADRs) in patients enrolled in the ON-TARGET study who were treated with the oral tyrosine kinase inhibitors (TKIs) axitinib or cabozantinib. The goal was to establish a preliminary data set and generate hypotheses for follow-up studies.
The pilot study shows that severe adverse drug reactions (ADRs) associated with treatment with the two TKIs are linked to distinct, time-resolved changes in circulating protein signatures, as measured in longitudinally collected liquid biopsy (plasma) samples. For the longitudinal analysis, specific pre-/during-/post-ADR triplets were formed to capture protein dynamics before, during, and after the resolution of severe ADR episodes. Eighty-eight selected samples with seven severe ADR episodes provided evaluable ADR triplets and formed the basis of the longitudinal analysis. This analysis identified nine proteins that were significantly upregulated during the UAW compared to the pre-UAW period. Seven of these proteins are closely associated with inflammatory signaling pathways, particularly with the development, proliferation, migration, and regulation of T cells.
BOTCAT was thus able to provide the preliminary data set and generate the hypotheses it was designed to produce, thereby demonstrating the feasibility of further studies in a larger cohort, such as the entire ON-TARGET study population.
The study was conducted by Jonathan P. Sirois under the direction of Prof. Dr. Oliver Scherf-Clavel at the Chair of Clinical Pharmacy and Pharmacotherapy at LMU Munich.
We would like to express our sincere thanks to the entire research team for their successful collaboration:
- Ludwig Maximilian University of Munich: Jonathan P. Sirois, Jonas Huhn, Prof. Dr. Oliver Scherf-Clavel
- Free University of Berlin & PharMetrX Graduate College: Fenja Klima, Prof. Dr. Charlotte Kloft
- University of Münster: Juliane Staudinger, Prof. Dr. Georg Hempel
- University of Bonn: Nadja Haas, Olga Teplytska, Prof. Dr. Ulrich Jaehde.
