KFO 179:  Biological Basis of Individual Tumour Response in Patients with Rectal Cancer

• Subject Area: Medicine
• Term: from 2007 to 2014
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 33996666

The Clinical Research Unit is a cooperation of surgeons, oncologists, radio-oncologists, medical oncologists, biologists and IT specialists who aim to develop a patient-adapted therapy of rectal cancer. In Europe and the US, colorectal tumours account for 15 percent of all cancers, with an increasing incidence. With more than 60,000 cases of newly diagnosed colorectal cancer per year, colorectal cancer is the second leading malignant disease in both male and female, and about half of them die due to this malignancy. About 30 percent of these tumours arise within a segment of 16 cm length, which is called the rectum.
Until recently, therapy was based on surgery followed by radio- and chemotherapy. As a consequence of subsequent clinical trials, the current therapy regimes include initial (preoperative) chemoradiotherapy followed by surgery and additional chemotherapy. Despite many advantages of this therapeutic strategy, the clinician is faced with the dilemma that the individual patient's tumour might react differently: a subset of tumours responds, some tumours barely shrink or don't respond at all.
This prompted us to initiate the Clinical Research Unit: Consisting of six independent subprojects and international partners, the goal is to combine specific scientific knowledge and expertise in order to develop an individualised therapy for each patient. Based on genetic analyses of patients with rectal cancer and their tumour-tissue, the participating researchers try to establish a more patient-specific approach for diagnosis and treatment, which is based on prediction of tumour response as well as prediction of individual side-effects. The final aim is to establish a tailored therapy to increase quality of life and rates of cure.

• DFG Programme: Clinical Research Units
• International Connection: USA

Projects

• Administration of the Clinical Research Unit devoted to "Biological basis of individual tumor response in patients with rectal cancer" (Applicant Ghadimi, B. Michael )
• Biomarkers for toxicity from and response to pre-operative radiochemotherapy: clinical, pharmacogenomic, and functional analyses (Applicant Wolff, Hendrik A. )
• Development of statistical and computational methods, tools, and infrastructure as well as data analysis, data management, and support for clinical researchers (Applicant Beißbarth, Tim )
• Identification of molecular profiles and markers for response prediction in rectal cancer and their clinical application (Applicant Ghadimi, B. Michael )
• Immuno-PET/CT analyses for prediction of tumor response induced by preoperative chemoradiotherapy (RT/CT) in locally advanced rectal cancer (RC; UICC stages II/III) (Applicant Meller, Johannes )
• Predictive and prognostic biomarkers in locally advanced rectal cancer, and prospects for risk-adapted tailoring (individualization) of multimodal therapy (Applicant Liersch, Torsten )
• Role of growth factor receptors and their downstream signaling pathways in the resistance or response of rectal adenocarcinoma to neoadjuvant radiochemotherapy (Applicant Burfeind, Peter )
• Socio-empirical and ethical analysis of patients' expectations and attitudes toward prognostic tests based on biomarkers in rectal cancer therapy (Applicant Schicktanz, Silke )
• The role of the AURORA-A oncogene in tumorigenesis and in the therapy response in colorectal and rectal cancer (Applicant Bastians, Holger )
• Treatment resistance of rectal cancers: identification and functional validation of novel therapeutic targets (Applicant Grade, Marian )

• Spokesperson: Professor Dr. Heinz Becker (†)
• Leader: Professor Dr. B. Michael Ghadimi