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Project

Metabolism as the key towards patient tailored treatment for rectal cancer?

Around 20% of patients with locally advanced rectal cancer (LARC) show a pathological complete response (pCR) after radiochemotherapy. Recent studies suggest that these patients could be spared from surgery. To omit surgery in these patients, careful selection of good responders after RCT and thus better understanding of the mechanisms behind these responses are needed. Evenmore, for patients that do not show a good response, an intensification of the current standard RCT is urgently needed both to improve overall prognosis and the rate of patients with pCR after RCT, hereby expanding the patient group eligible for organ preservation.

To accomplish selection of good responders and intensification of treatment, better predictive markers and new therapeutic targets are needed. Being an important hallmark of cancer cells, enhanced metabolism including enhanced glycolysis and lipogenesis, could offer such predictive markers and therapeutic targets.

Since one of the most important features of enhanced tumor metabolism is an enhanced lipogenesis, phospholipidomics analyses will be performed on a prospectively collected patient group to identify new metabolic predictive markers. Afterwards, these new metabolic predictive markers will be validated in another prospectively collected patient group. Enhanced glycolysis is another important feature of enhanced tumor metabolism. Imaging techniques such as 18-FDG-PET and DW-MRI reflect changes in metabolism that can be explored for predictive markers.

Recent data show that enzymes involved in FA synthesis are potential therapeutic targets for cancer treatment. If any targets are identified with the preceding phospholipidomics analyses, new therapeutic agents will be explored. Enhanced glycolysis in cancer cells could also be a therapeutic metabolic target. A recent study shows that the addition of metformin to RCT for patients with LARC led to a significant increase in pCR rate, disease free survival and overall survival. In vitro and in vivo experiments will explore the radiosensitizing potential of metformin when added to standard RCT.

In conclusion, numerous data collected by our group and others point towards an important role for metabolism in the response of patients with rectal cancer and suggest that metabolism might play a key role towards personalized medicine for patients with rectal cancer. Our goal is to develop a treatment protocol for LARC, incorporating all metabolic and imaging data.

Date:1 Aug 2015 →  15 Oct 2019
Keywords:rectal cancer, patient tailored treatment, Metabolism
Disciplines:Laboratory medicine, Palliative care and end-of-life care, Regenerative medicine, Other basic sciences, Other health sciences, Nursing, Other paramedical sciences, Other translational sciences, Other medical and health sciences
Project type:PhD project