Associated Principal Investigator, Department of Internal Medicine I
Prof. Dr. Christian Reinhardt and his team analyze genetic changes in tumor cells. A detailed understanding of the metabolic processes in tumors compared to those in healthy tissue allows molecular dependencies specific to cancer cells to be identified. This is how the group led by Christian Reinhardt works to identify new substances for tumor therapy. The team combines new therapeutic approaches with conventional treatments to systematically test the most successful line of attack.
Our research: Prof. Reinhardt and his team of scientists investigate tumor cells to detect the genomic changes that drive these cells. They use cell cultures and mouse models to identify agents that effectively inhibit these signaling pathways. Tailored treatment that only targets abnormal tissue protects the healthy cells that do not exhibit these genetic mutations, considerably minimizing unpleasant side effects for patients.
The research team uses cell lines with defined molecular changes and reactions to therapeutic agents in their search for ways to combat tumor cells. When a cell responds very effectively to an agent, the genomic characteristics of that cell are explored in detail. This allows genetic specifications to be optimally correlated with the respective therapeutic agent. The research team then tests the results on mouse models with the ultimate goal of speeding up the transfer of basic findings into new standard therapies.
Our successes: One of the working group’s most impressive achievements has been the initiation of clinical studies to test the new therapy. Patients are responding very well to treatment with the new active agents developed to target individual tumor cell genotypes. This is an excellent example of how successful translational research works at CECAD and the University of Cologne.
Our goals: The research team led by Prof. Reinhardt aims to develop novel therapies that will optimize treatment success and, as such, improve survival rates for different types of leukemia and solid tumors. Their ultimate goal is to advance the development of personalized therapies based on genetic changes in tumor cells. This would pave the way for the ultimate research objective: to increase therapeutic efficiency, while preserving healthy tissue as effectively as possible, thus prolonging survival while simultaneously improving quality of life.
Our methods/techniques: The research group’s standard methods are in vitro screening in combination with extensive validation in autochthonous mouse models. This approach almost ideally reflects the status in patients, which allows ‘real’ conclusions to be drawn regarding therapy. Once the results have been successfully confirmed, the next step is the transfer of the basic research findings into the clinic.
Figure 1: H/E stained tissue section of a tumor-bearing lung. NSCLC was induced in this KRASFrt.STOP.Frt;ROSA26::Frt.STOP.Frt.CreERT2;ROSA26::Lox.STOP.Lox.GFP animal via intratracheal AdenoFlp inhalation.
Figure 2: The animals depicted in (4) were treated with a one-week course of intraperitoneal 4OH-tamoxifen 4 weeks after inhalation to activate Cre-recombinase. In this system, Cre activity can only be induced in tumor cells, as only these cells have been previously exposed to AdenoFlp, which is necessary to remove the ROSA26::Frt.STOP.Frt cassette. Cre-mediated deletion of the ROSA26::Lox.STOP.Lox cassette allows for GFP expression, which was detected by flow cytometry of isolated tumor cells. Tumors were harvested 12 weeks after AdenoFlp.
Figure 3: Graphic representation of the different alleles used in this proposal.
Figure 4: Depicted are µCT images of KRASFrt.STOP.Frt;ROSA26::Frt.STOP.Frt.CreERT2;ROSA26::Lox.STOP.Lox.GFP animals that were intratracheally inhaled with an empty Adeno vector (top) or AdenoFlp (bottom). Lungs were imaged 3 months after inhalation.