Translational Gastrointestinal Oncology and Preclinical Models

Junior Clinical Cooperation Unit Translational Gastrointestinal Oncology and Preclinical Models

PD Dr. Johannes Betge

Patient derived organoids from a colorectal cancer patient, DNA (magenta), actin cytoskeleton (cyan), dead cells (yellow).
© dkfz.de

Carcinomas of the gastrointestinal tract are among the most common cancers. Despite recent advances in therapeutic options many cases cannot be cured, especially when the disease has spread and metastasized throughout the body. Our group therefore aims to develop novel, individualized therapies for patients with advanced gastrointestinal cancer and to analyze predictive markers, as well as mechanisms of resistance to therapies. For this, we are utilizing patient derived organoids (PDOs), up-to-date 3D cell culture models that we establish directly from our patients’ tumor or normal tissue biopsies. The organoids retain molecular characteristics of the original tissue and we can use them for functional analyses. We have established robotics-assisted high throughput-screening protocols that enable us to model drug response to hundreds of drugs simultaneously. We aim to translate these results of organoid-based drug screens back to bedside. Furthermore, we study tumor biology and the mechanisms of action and resistance of cancer drugs in tumors and organoids using high-throughput microscopy and single-cell sequencing. Thereby we aim to find markers for response and resistance that we further investigate in mechanistic studies. We are especially interested in the relevance of intracellular signaling pathways (most notably MAPK, IGF, PI3K/mTor) on tumor- and stem cell biology, drug response and development of drug resistance towards pharmacotherapies in colorectal cancer.

Prospectively, we aim to develop new treatments ex vivo in organoid models, most importantly using novel combinations of drugs, but also combining drugs and radiation therapy. Based on this, we will analyze their pertinent mechanisms of action and predictive markers. In a personalized approach using organoids and drug screening with clinically available anti-cancer drugs, we want to find individual therapeutic options for patients with advanced gastrointestinal cancer. We are currently testing this tailored approach in several clinical studies with our patients at the University Medical Center Mannheim (PROMISE studies).

Contact

PD Dr. Johannes Betge
Translational Gastrointestinal Oncology and Preclinical Models (B440)

Standort Heidelberg:
Im Neuenheimer Feld 580
Technologiepark 3
69120 Heidelberg

Standort Mannheim:
Universitätsklinikum Mannheim
II. Medizinische Klinik
Theodor-Kutzer-Ufer 1-3
68167 Mannheim

E-Mail: j.betge@dkfz.de

Selected Publications

  • Betge J*, Rindtorff N*, Sauer J*, Rauscher B, Dingert C, Gaitantzi H, Herweck F, Miersch T, Valentini E, Hauber V, Gutting T, Frank L, Belle S, Gaiser T, Buchholz I, Jesenofsky R, Härtel N, Zhan T, Fischer B, Breitkopf-Heinlein K, Burgermeister E, Ebert MP, Boutros M. (2019) Multiparametric phenotyping of compound effects on patient derived organoids. bioRxiv, 660993, doi: https://doi.org/10.1101/660993.
  • Herrmann S*, Zhan T*, Betge J*, Rauscher B, Belle S, Gutting T, Schulte S, Jesenofsky R, Härtel N, Gaiser T, Hofheinz RD, Ebert MP, Boutros M (2019). Detection of mutational patterns in cell free DNA (cfDNA) of colorectal cancer by custom amplicon sequencing. Mol Oncol; 13:1669-83. (*co-first authors)
  • van Dijk E, Biesma HD, Cordes M, Smeets D, Neerincx M, Das S, Eijk PP, Murphy VS, Barat A, Bacon O, Prehn JHM, Betge J, Gaiser T, Fender B, Meijer GA, McNamara DA, Klinger R, Koopman M, Ebert MPA , Kay EW, Hennessey BT, Verheul HMW, Gallagher WM, O'Connor DP, Punt CJA, Loupakis F, Lambrechts D, Byrne AT, van Grieken NCT, Ylstra B. (2018) Loss of Chromosome 18q11.2-q12.1 Is Predictive for Survival in Patients With Metastatic Colorectal Cancer Treated With Bevacizumab. J Clin Oncol, 36:2052-60
  • Zhan T, Belle S, Valentini E, Herrmann S, Miersch T, Li M, Gaiser T, Boutros M, Ebert MP, Betge J. (2020) Cancer-Associated Mutations in Normal Colorectal Mucosa Adjacent to Sporadic Neoplasia. Clin Transl Gastroenterol, 11:e00212.
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