2023-06-14 02:13:50
A. Background and problem statement
Rectal cancer is treated with a combination of chemotherapy and radiation followed by surgery. If, after the pre-treatment, for example by endoscopy, it appears that the tumor has completely disappeared, the radical operation can be dispensed with and intensive monitoring can take place instead. However, both during endoscopy and during a possible operation it is difficult to recognize the tumor and remove it in its entirety, partly because a lot of scar tissue has been created by the chemotherapy and radiation.
B. Research direction/proposed solution
This project is working on methods to make tumors more visible during operations and endoscopy. This is done by developing fluorescent substances that bind specifically to the patient’s tumor cells and that can be administered before surgery or endoscopy. The fluorescence is not visible to the human eye, but it is visible with a special camera. In this technique, the development of a contrast agent that is specific for the tumor cells and does not or hardly bind to surrounding healthy cells is important.
C. Relevance
An improved detection of rectal cancer during endoscopy, especially after pre-treatment, will contribute to a better selection of patients for organ-sparing treatment. On the one hand, unnecessary operations can be prevented, which contributes to an improved quality of life. In addition, during the intensive monitoring of patients after chemotherapy and radiation, a possible recurrence of the tumor can be detected in good time. If patients need surgery, this technique can also ensure that the tumor is completely removed during surgery.
D. Research Questions
The aims of the research are:
1. To identify proteins that are present in higher amounts on the tumor than on normal surrounding tissue.
2. Developing fluorescent peptides that can bind to these proteins and thus make the tumor visible.
E. Research design
Special software is used to search scientific databases for proteins that occur on the cell surface of rectal tumors, but not on normal cells in the vicinity of the tumor. Using other software, small proteins (‘peptides’, which can be easily synthesized) are then predicted, which can bind to them. These are then synthesized and provided with a fluorescent substance. Using cultured tumor cells, it is determined which fluorescent peptides bind sufficiently to those proteins on the tumor cells but not to healthy cells. In this way, peptides are selected that can ultimately be used clinically in the detection and removal of rectal cancer.
F. Expected Outcomes
We expect to develop at least one fluorescent peptide that can make rectal cancer visible. If this is successful, we can also implement this development technique for other tumor types.
G. Description of steps required to implement result
All consortium partners have the expertise and experience to translate the obtained results to the clinic, with the aim of making our fluorescent peptide(s) available to patients as soon as possible. This requires clinical phase 0, 1, 2 and 3 studies. Both the LUMC and the CHDR can facilitate this.
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