Our work

Professor Helmout Modjtahedi is shown in the Faculty of Science, Engineering and Computing with his PhD student Said Khelwatty. Together with Dr Sharadah Essapen (Consultant Oncologist, St. Lukes Cancer Centre), Dr Alan Seddon (Kingston University) and their colleagues at Royal Surrey County Hospital, they have been investigating existing and novel treatments for cancer of the colon and rectum, known as colorectal cancer. By examining colon cancer specimens from patients, the research aims to identify specific markers which could indicate how patients will respond to treatments with anti-cancer drugs. Their results suggest that the growth and aggressive behaviour of some colorectal cancers may be significantly influenced by a specific group of growth receptors on the cancer, known as the HER family. Furthermore, the activity of more than one member of this growth factor receptor family seems to be prominent in colorectal cancers. Consequently targeting of only one member of this family will not be sufficient for the eradication of such tumours and can contribute to the poor response rates and development of resistance to therapy, often seen in patients. Their research has also shown that treatment of colorectal cancer cells with a new agent called afatinib, which blocks the activation of all four members of the HER family, is more effective than other agents in inhibiting their growth in the laboratory.

In order to understand why it is that, after several cycles of chemotherapy or treatment with other agents, we tend to see resistance to these agents, they developed several drug resistance colorectal cancer cells in the laboratory by treating colorectal cancer cells with the increasing doses of various drugs up to one year in the laboratory. Their preliminary results suggest that tumours which develop resistance to one type of drug, for example an antibody based drug, are still sensitive to treatment with another class of anti-cancer drug such as afatinib which is a small molecule tyrosine kinase inhibitor and vice versa. More recently, they have also reported the potential of two anti-EGFR antibodies with potential in the identification of a more specific group of colorectal cancer patients who are more likely to benefit from therapy with antibody based drugs such as cetuximab and panitumumab. Professor Modjtahedi said "We are immensely grateful to the BRIGHT charity for funding this important study. We intend to pursue these important findings to help improve the response, survival and cure rates in patients with colorectal cancer. Most of the experimental work has been carried out by Said at Kingston University research laboratories. Examination of the tumour specimens from colorectal cancer patients was conducted at the Department of Histopathology, St Luke’s Cancer Centre, Royal Surrey County Hospital. Said’s other PhD supervisors on this project were Dr Sharadah Essapen (Consultant Oncologist) and Dr Alan Seddon. Said submitted his PhD thesis in December 2012. They have already presented their findings at several national and international cancer conferences (Berlin, Liverpool, London, Washington), with several publications in cancer journals and several manuscripts in preparation.

On another project, Dr. Rachel Gabitass has researched potential new targets for treatment of upper gastrointestinal cancers (oesophageal, gastric, pancreatic). She has investigated Myeloid-derived supressor cells and T regulatory cells which are increased in certain of these cancers and are thought to supress the patient's normal immune system, so that it does not kill the cancer cells as it should (by testing patient's blood and tumour samples, she compared these cell levels with the normal levels found in a person without cancer). Then she has shown  that certain types of chemotherapy can reduce these levels. The results of her work have now been published.

The presence of certain cells will always thwart any attempt to harness a patient's immune system in cancer. A thorough understanding of the dynamics of these 'immunosuppresive' cells is therefore essential to developing strategies to overcome their effects. These strategies will not only lead to an enhancement of the natural immunity that patient's have against their own cancers but will also be critical to the targetting of treatments with specific cancer vaccines.

In particular, pancreatic cancer is characterised by its late presentation, aggresive local and distant growth and is associated with profound immune suppression due to inhibitory immune cells. BRIGHT is sponsoring an ongoing study of pancreatic cancer at the University of Surrey post graduate medical school (PGMS). The first step has been to develop an 'in vivo' testbed model as a way of being able to test the effectiveness of existing treatments. This has now proved successful, as described in detail here.

The second step has been to focus on the role of HOX genes in pancreatic cancer. PHD student Sophie Gray has been assessing levels of HOX genes in this type of cancer and secondly to block HOX gene expression using a protein, HXR9. Results showed that HOX gene expression was significantly higher in metastatic pancreatic cancer compared to normal pancreas and that antagonising HOX genes with HXR9 induced cell death in vitro. Sophie presented her findings to date at the American Association for Cancer Research (AACR) annual meeting in April 2013 (see here). Work is continuing to research a link between HOX gene signatures and patient survival.

Future research projects are planned, in particular by Dr. Alexandra Stewart, who wishes to look into the improvement of radiotherapy dose delivery in pelvic cancer. She is interested in the role of brachytherapy in rectal cancer, which involves placement of radioactive sources within (or very close to) the cancer to give a highly conformal radiotherapy treatment.