Over 4,000 people are diagnosed with new cases of brain or central nervous system (CNS) cancer every year in the UK. Glioblastomas are the most common and aggressive form of brain tumour in adults. Research at the CRUK Cambridge Centre is focused on understanding the different types of brain tumours that develop in both adults and children, finding the most effective ways of diagnosing brain tumours as early as possible, developing new treatments and monitoring how tumours are responding to treatment.
The Centre is coordinating a number of clinical trials for adults and children with cancer of the brain or spinal cord. One of these trials is testing a new tool to help surgeons remove as much of brain tumour as possible and potentially improve the survival rates of patients. Patients with glioblastoma are given a drink, which makes the tumour cells glow pink under ultra-violet light. This allows the surgeon to distinguish tumour from normal brain allowing more tumour to be removed while improving patient safety. Discs with a drug that kills tumour cells are then implanted in the space left after the tumour has been removed, to target any tumour cells left behind.
We have recently developed a real-time multiple sampling scheme to interrogate high-grade glioma during surgery. FGMS (Fluorescence-Guided Multiple Sampling) is based on fluorescence-guided resection technology to obtain spatially distinct tumour biopsies from individual tumours in real time, during cytoreductive surgery Figure. We can use these data to dissect intra-tumour heterogeneity, identify clonal diversity and infer tumour evolution. Little is known about the impact of intra-tumour heterogeneity on tumour evolution, growth and the consequences of such heterogeneity on the emergence of resistant disease. This is an important problem in brain tumour research because it is the emergence of recurrent treatment-resistant disease that kills patients and it is variability in this biological process that is responsible for variation between individual patients.
The Cambridge Cancer Centre is developing novel imaging biomarkers, suitable for use in routine clinical practice, which will identify disease instability and monitor and predict treatment response. A new collaborative EPSRC/CRUK-funded strategic programme undertaken in conjunction with the Manchester Cancer Research Centre has established the CRUK & EPSRC Cancer Imaging Centre in Cambridge & Manchester to develop ‘imaging signatures’ of different tumours and their response to treatment. The challenge is to reliably identify ‘imaging signatures’ that reproducibly identify pathological processes such as cell proliferation or brain invasion. This will have a major impact on the development of improved non-invasive techniques for diagnosis, treatment, identification of early treatment response and early detection of tumour resistance.We are also developing biomarkers for use during operations to help surgeons remove cancer cells more effectively and safely. This will help radiotherapy and chemotherapy to work more effectively to improve patient survival.
To date, novel treatments for glioblastoma have mainly been developed in conventional, established glioma cell culture systems then tested in small animal models in vivo. With the exception of temozolomide, these treatments have uniformly failed to improve outcomes in the clinic. We propose that these models are inadequate and generate misleading data. The objective of the CRUK Cambridge Centre is to establish and validate novel models that recapitulate as closely as possible what happens to patients and significantly increase the likelihood of novel therapies having clinical benefit. To achieve this we will integrate advanced surgical sampling, intracerebral microdialysis of patients and high-efficiency cell derivation techniques to generate genetically defined and clinically annotated tumour samples, cancer stem cells and xenografts. We will develop corresponding models and patient-specific cell libraries. We will use these data for high-throughput drug screening and build inter-disciplinary collaborations to exploit fully our biological, radiological and clinical data.
Correct patient selection and optimal trial design is critical for the successful clinical evaluation of new treatments. In particular, it is essential that the right patient receive the right drug and appropriate outcome measures recorded to evaluate benefits to patients in terms of survival, quality-of-life and complications. The CRUK Cambridge Centre has established a dedicated glioma clinic to provide patients with access to experts including oncologists, surgeons and specialist nurses. This multidisciplinary team can help and support patients throughout their treatment and recruit them into clinical trials wherever possible.
The in-depth understanding of brain cancer provide by the huge range of expertise in the Centre will be used to guide future management and care, and facilitate the evaluation of novel therapeutic approaches tailored to the most appropriate group of patients. In this way we will rapidly and efficiently evaluate markers of detection, diagnosis, response and progression in patients.
Richard Gilbertson and Nicky Huskens discuss progress made so far with the Tessa Jowell Brain Cancer Research Mission ahead of the next committee meeting in November...