Two out of five bowel cancer patients do not respond to current treatments, and those whose cancer spreads to other organs face a particularly poor outlook. This fellowship tackles that gap by using genetic engineering to identify the specific vulnerabilities that allow cancer cells to grow and spread inside the body. The researcher has already developed a novel way to genetically engineer cancer cells and track which genes control their behaviour in a living host with a functioning immune system—something traditional lab-dish experiments cannot replicate. In this renewal period, the work will focus on two questions: how poor-outlook cancers hijack the immune system to aid metastasis, and how existing drugs could be repurposed to treat these aggressive tumours more effectively. If successful, the research could identify new drug targets and clinical strategies for the 40% of bowel cancer patients who currently lack effective options. The tools and methods developed—particularly for genetic engineering and transplantation in immune-competent models—will be shared with national research centres, potentially shifting how cancer scientists study metastasis. By working directly with pharmaceutical and biotechnology companies, the project aims to fast-track findings toward patient benefit rather than leaving them in the academic literature.
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Context and challenge Cancer of the bowel is the 4th most common cancer diagnosis in the UK. The survival rate for bowel cancer has doubled in the last fifty years, with three out of five patients responding well to treatments and showing prolonged survival. Despite this, two out of five patients will not respond to current treatments. Patients with cancer spreading from the bowel to other organs have a particularly poor outlook. We therefore need to research and develop new treatments for these patients that lack good clinical options. This fellowship aims to tackle this problem by using genetic engineering to find crucial vulnerabilities in cancer cells to stop them growing and spreading. We hope to use this information to contribute to the development of new treatments for bowel cancer. Aims and objectives The initial phase of this fellowship allowed the development of an entirely novel way of using genetic engineering of cancer cells to identify genes that control cancer cell growth or spread in the body. In the renewal period, we aim to delve deeply into how these genes act and understand what the best way is to interfere with them to treat cancer. We propose the following work: Characterise the way poor outlook cancer cells hijack the immune system to help cancers spread. Use genetic engineering to work out how best to use drugs we already have in the clinic to better treat bowel cancers. Applications and Benefits Continued funding of this fellowship for the renewal period will have applications across academic research, public health practice and the biotechnology and pharmaceutical industries. The wider research community The tools and knowledge that we develop on how to perform genetic engineering and cancer cell transplantation in hosts with a functioning immune system will be shared with the scientific community and national centres to allow others to perform this approach. The data generated will be crucial to understand whether the previously described traditional in-a-dish approaches typical of cancer research have missed key information compared to examining tumours in the body. Public health This research aims to identify new potential targets and clinical treatments for patients lacking these options, by developing new ways to study cancer that focus on understanding how cancer cells spread. By examining drugs currently in development or clinical use, this project has the potential to influence how poor outlook patients are treated. Biotechnology and pharmaceutical industries By working directly with the biotechnology and pharmaceutical industries and making use of therapies already developed this work is aimed at fast-tracking our findings towards patient benefit. The public This fellowship aims to understand how cancers spread and identify vulnerabilities in cancer cells that might be used for therapies. Given the global health burden of bowel cancer, with 40% of those patients lacking effective treatments, this work aims to improve global cancer survival rates.
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