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Cancer Immunotherapy
Largely due to increases in funding there are numerous, continuing developments in the area of immunotherapy and prostate cancer treatment. A recent article published by prostatecanceruk.org highlighted the latest research of some potentially exciting studies which may be of interest.
About 1 in 6 cases of prostate cancer have a lot of inflammation in the surrounding area and this means they are more likely to spread and recur after treatment. Professor Richard Bryant and Dr Eileen Parkes believe that this may be due to triggering a chain of events in the cell known as the STING pathway.
Previous work by Professor Bryant and Dr Parkes found that prostate cancers which have activated the STING pathway have a lot of immune cells present. They believe that the STING pathway allows the cancer to hijack the immune system, so rather than working to destroy the cancer, the immune cells help it to grow more aggressively.
In this project, the team want to understand the role of the immune system in cases of prostate cancer with inflammation, particularly how the STING pathway responds to radiotherapy. If successful, this could lead to clinical trials of treatments that can be combined with radiotherapy to reduce the recurrence of prostate cancer.
Professor Bryant : “Radiotherapy is an effective treatment for prostate cancer, but early evidence suggests it causes an immune response that helps make any surviving cancer cells more aggressive and likely to spread.”
Dr Parkes : “By understanding how radiotherapy triggers prostate cancer to hijack the immune system in this way, we hope to find treatments that can stop this from happening and reduce the chances of the cancer returning.”
I myself, have just (today) contacted Professor Bryant, Dr Parkes, University of Oxford as I am interested in participating in any current, or future trails in this area and,or from imparting my own ‘case’ details. After a radical proctectomy, I suffered reoccurrences and have undertaken SABR, Proton Beam Radiotherapy treatment.
Although Dr Parkes and Professor Bryant are working together on the STING study they also have ongoing, individual, Immunol related research projects.
Dr Parkes (The Parkes Lab) is currently actively researching the following areas –
- Understanding resistance mechanisms to immune-targeting treatments in cancer
- Characterisation – the role of DNA repair deficiency and immune activation in tumour initiation, progression and response.
The Parkes Lab
They are studying intrinsic inflammatory pathways in cancer. Important immune pathways, present in all cells, that act as emergency response pathways to viral infection. However, in cancer, these pathways can be rewired and hijacked by the tumour to promote growth, invasion and metastasis.
Previously we have identified the importance of the STING pathway in DNA repair deficient cancer. We also know that the STING pathway can be used to drive metastatic spread in some cases. As the STING pathway is crucial for response to standard anti-cancer therapy as well as newer immunotherapies, understanding how this pathway is rewired in cancer can help us develop new treatment approaches.
A multi-pronged approach to answer the important question of immune activation in cancer – working in vitro, in vivo and with samples donated from people with cancer.
Current Projects are addressing the following topics –
(1) Regulation of 2’3’cGAMP channels in the tumour microenvironment: Various channels have recently been identified regulating the uptake of 2’3′ cGAMP (the stimulating molecule of the STING pathway) in to distinct cell types. In this project, the distribution of these channels and activity will be characterised.
(2) Crosstalk between STING and the inflammasome pathway in cancer: The production of IL-1B is a crucial contributor to metastasis in cancer. However the role and relative contribution of the STING pathway is unclear. In this project, students will have the opportunity to clarify this relationship and determine its importance in cancer growth, progression and response to therapy.
(3) Characterisation of the immunomodulatory effects of therapy in oesophageal cancer: Oesophageal cancer remains one of the deadliest cancers, and the incidence of this cancer is increasing in the UK. In this study, work with samples donated from people with cancer to understand how the immune response is modulated during the course of anti-cancer therapy, identifying potential resistance mechanisms for further exploration.
Each of these topics includes work in vitro, in vivo and/or using patient samples. Molecular biology techniques such as CRISPR are commonly employed in our group, generating novel models for study in vitro and in vivo.
Professor Bryant has published several papers, clinical studies and reviews including a paper reviewing the use of Aspirin as a prostate cancer treatment of which I have posted a separate blog.
Immunotherapy Blood test
Developing a blood test that could show who will benefit from immunotherapy, Professor Aled Clayton, University of Cardiff
Though immunotherapy is an exciting field with huge amounts of potential, immunotherapies currently only work in rare cases for prostate cancer and it’s not clear why.
Professor Aled Clayton at the University of Cardiff seeks to understand why some men benefit from these treatments, but others don’t. He believes that the way prostate cancer changes its surrounding environment may affect the immune system response.
Previous work from Professor Clayton has shown that prostate cancer tumours release small packages of molecules into the bloodstream, which can stop immune cells from working. As part of this project, the team will develop new methods to identify these packages in the blood.
Professor Clayton : “This project will ultimately help us design approaches to treat prostate cancer by making immunotherapy a more effective and predictable treatment. In the future, we hope this could lead to blood tests which could check whether a particular form of immunotherapy is likely to work or not. This would help to ensure men are receiving the best possible treatment for their cancer.”
Lu-PSMA Research
Combining targeted radiotherapy with immunotherapy for a double jolt to the immune system, Professor Katherine Vallis, University of Oxford
A promising new type of targeted radiotherapy treatment may soon become widely available for men with advanced prostate cancer, but we don’t fully understand its wider effects.
The new drug called Lu-PSMA works to ‘seek and destroy’ cancer cells. One part of the drug attaches to a protein called a PSMA receptor, which is commonly produced by prostate cancer cells. This brings the cancer cells into close contact with the other part of the drug – a radioactive Lutetium-177 atom.
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