Influence of chromatin organisation on the therapeutic response of rectal cancers to neoadjuvant treatment

Summary

Background

Rectal cancer (affecting the lower part of the bowel) is a common and life-threatening disease. Concerningly, it is becoming more common in young adults under 50 years old. In these people it is more advanced at diagnosis, and as a result a combination of chemotherapy and radiotherapy is required to shrink the cancer before it is removed with an operation. How tumours respond to this treatment is highly variable. Some people get limited benefit despite it leaving them with major side effects, whereas other tumours disappear completely. At present, our understanding of what drives these differing responses is incomplete and additionally there are no ways of predicting who will or will not respond to this treatment and gain benefit from it.

Research approach

To understand this better, we will study how some rectal cancers change the way their genes are packaged (called epigenetic changes) to make themselves more resistant to treatments. Laboratory tests will be performed on cells to see how modifying gene packaging controls how rectal cancers respond to irradiation. To ensure that the changes observed in cells in the laboratory correspond to those found in patients' tumours we will perform experiments to compare the two sets of results.

Expected impact

This work will improve our understanding of how rectal cancers respond to treatments. Our long term goal is to use these insights to further develop how we match these important treatments to those who will benefit from them.