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Cancer Sciences

a The Division of Cancer Sciences encompasses research groups looking at both basic and translational cancer research.

Targeted Cancer Therapy Group

In addition to killing tumour cells, conventional cancer therapies such as chemotherapy and radiotherapy kill all dividing cells in the body resulting in a wide range of unwanted side effects. Targeted therapy blocks the growth of cancer cells by interfering with specific targeted molecules present only in tumour cells thus with the ultimate aim of  achieving a much more efficient and  specific treatment which only kills tumour cells and thus reduces the side effects experienced by the patients. The Targeted Cancer Therapy group, based at The University of Surrey and led by Professor Pandha, are working on several projects:

Viral Therapy:

Investigating so-called oncolytic viruses (viruses that solely replicate in cancer cells causing them to die) including herpes simplex virus (HSV), coxsackie virus and reovirus in bladder and prostate models. A clinical trial has recently been completed which used Coxsackie A21 virus in conjunction with mitomycin C to target and kill non muscle invasive bladder cancer cells. 

Tumour slice model:

Pioneering work is being carried out to develop a unique and novel model to test drugs in vitro. The tumour slice model uses a vibrating microtome (rather like a meat slicer) to slice a primary human tumour, taken fresh from the operating theatre, into wafer thin slices which can then be cultured for many days in vitro. This allows drugs and other novel compounds to be tested in an environment in which the architecture and tumour cells are representative of the tumour in a much better way than using tumour cell lines in vitro.

Peptide therapy:

A novel peptide, named HXR9 has been developed and shown to kill a range of tumour cell types in vitro. The peptide has also been shown to be effective in killing tumour cells in animal models. The peptide is now being tested in the tumour slice model using a variety of tumour types and plans are to test the peptide in a clinical trial. A small molecule mimic of HXR9 is also being tested.

Immunotherapy:

It has been shown that T cells found in tumours are often in an exhausted state. In order to reverse the process of T cell exhaustion in tumours we are analysing a range of tumours, in particular kidney tumours, to assess the state of their T cell populations with the ultimate aim of trying to reactivate them so that immunotherapeutic approaches are more effective.

Novel therapeutic strategies for castrate resistant prostate cancer (CRPC)

Research into the identification of molecular/cellular mechanisms that lead to the development of castrate resistant prostate cancer (CRPC). In particular  the development of therapeutic strategies to inhibit the oncogenic transcription factor the Androgen Receptor (AR) which is the major driver of the disease with an overall goal to eradicate CRPC or delay its onset.

Biobanking:

Setting up a bio-repository and accompanying 'database' of 300 patients with all stages of prostate cancer to allow longitudinal blood sampling whilst on different treatment programs, and enable banking and analysis of serum and DNA at 6 monthly intervals.

Novel Cancer Trials:

A clinical team of 12 staff are developing a large programme of clinical research directed at improved treatment for cancer, understanding the causes of cancer and developing new methods of detection.

  TRIOC - Ovarian Cancer

TRIOC has now been open in UK sites since 26th November 2013 and is recruiting fast.  There are currently 8 sites open to recruitment with 85 patients registered/randomised. The trial has been amended to a Phase II single arm trial and no further patients are recruited into the placebo arm. Recruitment continues up to end of October 2017. The study treatment is well tolerated and there are no safety concerns.  http://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-trial-looking-trovax-ovarian-cancer-primary-peritoneal-cancer-fallopian-tube-cancer-has-come-back-trioc

 EDMONd

 A very large proportion of women with advanced ovarian cancer may develop a blockage in the bowel, which is often inoperable. Bowel obstruction causes significant issues to women, stopping them from being able to absorb essential food and nutrients. Providing the right nutritional support for women with inoperable bowel obstruction is extremely challenging.

Elemental Diet (ED) provides nutrition in the form of amino acids and easily digestible nutrients that are almost totally absorbed in the upper small intestine and could be of benefit to women. The initial concept is the product of the space race and was originally developed by NASA for astronauts.

The aim of the project is to assess whether Elemental Diet would be tolerated by women with inoperable bowel obstruction. The study will also assess whether this diet can meet some of the women’s nutritional requirements and have a positive impact on their quality of life. If successful, this research would be a big step towards improving the quality of life and would help women live longer.

Links: http://www.targetovariancancer.org.uk/our-research/our-research-projects/edmond-diet-and-nutrition-patients-inoperable-malignant-bowel

http://ctu.surrey.ac.uk/trials/edmond-feasibility-study-elemental-diet-alternative-parenteral-nutrition-ovarian-cancer

Dr Tony Dhillon BSc, MB BS, FRCP, PhD

Senior Lecturer in Oncology, University of Surrey and Consultant Medical Oncologist, Royal Surrey County Hospital, Guildford, Surrey, UK 
High POLE study 

A Phase 2 trial of neoadjuvant nivolumab and ipilimumab in operable microsatellite instability high (MSI-H) or POLE exonuclease domain-mutant colon cancer (CC) -High POLE TRIAL.

 Primary Objective:

To determine preliminary evidence of efficacy after administering neoadjuvant nivolumab and ipilimumab over a 6-week schedule in operable MSI high or POLE exonuclease domain mutant colon cancer (CRC) patients

Secondary Objectives:

•       To assess the safety (2 treatments of combination Nivolumab and ipilimumab 3 weeks apart) schedule in the neo-adjuvant setting

•       To report the effects of Nivolumab and ipilimumab in a neo-adjuvant setting through PFS, OS, pathological response and Quality of life. Translational work looking at immune related outcomes in MSI-High and POLE mutant CRC pre-and post-checkpoint inhibition. Investigations will include:

Profiling of circulating and tumour-infiltrating immune cell populations

Tumour phenotyping

TIL gene expression analysis

Tumour sequencing and prediction of neo-epitopes

Tissue for tissue microarray (TMA (paired)

The study will recruit about 50 patients and will be based at the Royal Surrey, Oxford and Leicester.

The translational research programme will be based at the University of Surrey in Prof Hardev Pandha’s laboratory and at the Wellcome centre of Human genetics at the University of Oxford.

The research will be funded by Bristol Myers Squib.

POLEM Study

Avelumab plus 5-FU based chemotherapy as adjuvant treatment for stage 3 MSI-High or POLE exonuclease domain mutant colon cancer: A phase 3 randomised study.

Primary objective

To compare the efficacy of adjuvant Avelumab and standard 5-FU based chemotherapy with standard 5-FU alone in operable stage 3 MSI high or POLE exonuclease domain mutant colon cancer (CRC) patients in terms of disease free survival (DFS)

Secondary objectives

  • To compare the effectiveness of adjuvant Avelumab and standard 5-FU based chemotherapy with standard 5-FU alone in terms of overall survival (OS)
  • To compare the safety of adjuvant Avelumab and standard 5-FU based chemotherapy with standard 5-FU alone
  • To determine the cost-effectiveness of adjuvant Avelumab and standard 5-FU based chemotherapy with standard 5-FU alone
  • To compare the Health-related quality of life (HRQoL)

 Proposed translational research programme will look at :

  1. Predictors of Avelumab benefit
  2. Circulating immune correlates of Avelumab therapy
  3. Circulating DNA markers as predictors of clinical outcome
  4. Germline predictors of Avelumab toxicity
  5. Determining the mechanistic basis of response and resistance to immuno-oncologic therapy using preclinical models.

The trial will recruit about 406 patients and will run in about 30 centres nationwide.

The translational research will be based at the University of Surrey, Oxford and the Institute of cancer research (ICR).

The study will be funded by Merck.

My main collaborator are Dr David Church at the University of Oxford and Professor David Cunningham at the Royal Marsden Hospital/Institute of Cancer Research.

Find out more at:

http://www.surrey.ac.uk/microbial/Research/cancer/

Blackbourn Laboratory

Infectious agents, including viruses, are associated with up to 20% of human cancers. The Blackbourn laboratory, led by Professor David Blackbourn and based at the University of Surrey, studies two such viruses that are responsible for causing cancer: Kaposi's sarcoma-associated herpesvirus (KSHV) and Merkel cell polyomavirus (MCV or MCPyV). Their particular interests lie in how such viruses cause disease, evade the immune response and interact with the DNA damage response. Their main research topics are:

  • How KSHV interacts with the DNA damage response.
  • How KSHV modulates the type I interferon (alpha & beta) response.
  • How KSHV deregulates antigen-specific T cell responses.
  • What are the consequences of KSHV infection on endothelial cell biology, including cell-cell interactions and regulating leukocyte recruitment?
  • Understanding the tumour microenvironment and how it contributes to the pathogenesis of Merkel cell carcinoma.
Find out more at:

http://www.surrey.ac.uk/fhms/people/atoz/100985/index.htm