Our Achievements - Research

RESEARCH UNDERTAKEN BY OUR RESEARCH FELLOWS

When we give chemotherapy to patients whose bowel cancer has spread to the liver, the cancer in the liver often shrinks leaving behind a rim of tissue that can be seen on certain MRI scans.   We call this rim of tissue the ‘halo’ as it often appears as a spherical hue surrounding the cancer with a different appearance to both that of cancer and normal liver tissue.

In his work, our trust research fellow examined the genetic makeup of this halo tissue with that of cancer tissue and normal tissue in patients undergoing surgery.   By studying the differences between these tissues, we concluded that the genetic makeup of ‘halo’ tissue is closer to normal tissue than to cancer tissue.

As we traditionally excise cancers with a wide margin of normal tissue to ensure that no cancer is left behind, the work supported the practice that halo tissue can be considered as normal and included in the margin.   The consequence of his work is that cancers which were once thought to be unresectable because a wide enough margin couldn’t be achieved, could be resected if the tumour shrinks sufficiently to leave a halo of tissue that provides enough margin.

Genetic markers for secondary cancers of colonic origin

During an analysis of the genetic mark-up of different cancer tissues, we identified 2 genes that were highly expressed in secondary cancers from a bowel origin.   The gene S100A11 when highly expressed, could identify these secondary cancers with 96% accuracy and the gene ATP11B with 100% accuracy.

If these genes can be detected in the blood of patients being investigated for bowel cancer, we may be able to confidently identify those patients who already have secondary spread.   Furthermore, if the function of these genes proves to contribute towards the spread of the cancer, we may be able to block and hinder their behaviour.   Work on the genes is ongoing.

Chemotherapy induced genetic change

Analysis of liver tissue that had received chemotherapy before the operation, showed that even in normal tissue, genes linked with inflammation and apoptosis (automated cell-death) were increased, complementing previous clinical studies that suggested chemotherapy was toxic to the liver and adversely affected post-operative mobidity and mortality.

There was, however, no difference in the genetic changes seen within the cancer tissue whether 3 to 6 cycles or 8 to 12 cycles were used suggesting that a shorter course was just as effective as a longer course without the increase in side effects.

Effect of neoadjuvant chemotherapy (ie. Chemotherapy prior to surgery) on the liver

In patients due to have liver surgery for metastases from bowel cancer, we often give a course of chemotherapy to shrink the tumours before operating.   One side effect of chemotherapy is that it damages normal liver tissue too.   We have designed a randomised study that will compare the degree of liver damage caused by the 2 main combinations of chemotherapy we use.   Because it is important to preserve the function of the remaining liver in order to avoid liver failure, this study can give us important information on which combination chemotherapy is better and whether we are giving too many cycles.

The study is being conducted in collaboration with our oncology specialists. It has been approved by the Trust Research and Development Committee and by the ethics board.   We hope to start recruiting patients within a month.

Studies of circulating tumour cells

Circulating tumour cells are cells that have escaped from the primary cancer that are found in the blood.   They are an integral step in forming secondary tumours elsewhere in the body

  • By detecting whether numbers of these cells are decreasing during neoadjuvant chemotherapy, we can examine the effectiveness of our chemotherapy regimens and try to predict which patients are likely to develop recurrence and therefore decide if further chemotherapy is needed afterwards.
  • By using genetic analysis techniques at the University of Surrey we hope to isolate and culture these cells alongside cancer cells retrieved from the liver tumours themselves.   The hope is to analyse the genetic make-up of these cells and identify the genes that are consistently found in more aggressive tumours.   In future, we should be able to identify these genes early on when the primary cancer is diagnosed and treat these patients more aggressively (for example with early chemotherapy or more frequent follow-up scans) so that we prevent or treat recurrences more successfully.

Currently, we are testing the technology at the University’s post-graduate medical school to check that we are retrieving the correct cells from blood samples.   At the moment we are working with spiked samples (blood samples we have intentionally spiked with cancer cells) and are retrieving 60% of cells successfully.   We think we can improve this retrieval rate to 90%.   We already have ethical approval for this study.