Radiotherapy can paradoxically make some surviving cancer cells more aggressive, actively driving them to spread throughout the body rather than killing them. This fellowship targets that dangerous side effect in two cancers with especially bleak outlooks: glioblastoma and pancreatic cancer. The problem is that while radiotherapy remains a cornerstone treatment for many solid tumours, a growing body of evidence shows it can trigger a "pro-metastatic" response in cells that survive the radiation. This means the very treatment meant to cure patients may inadvertently fuel the disease's spread. The biology behind this effect is complex and poorly understood, leaving clinicians unable to predict which patients face heightened risk or how to counteract it. If this research succeeds, it could fundamentally change how radiotherapy is delivered. The team has already identified potential chemotherapeutic inhibitors that block radiation-driven metastasis. The renewal phase will push these candidates toward clinical testing, while also mining clinical data to understand the real-world impact on pancreatic cancer outcomes. For patients with glioblastoma and pancreatic cancer—where survival rates have barely budged in decades—this could mean radiotherapy becomes both safer and more effective, directly improving symptom management and extending life.
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Context and Challenge Radiotherapy is an effective and potentially curative treatment that is used for many solid cancers. However, a growing body of pre-clinical evidence indicates that radiotherapy may also induce a 'pro-metastatic' effect in any cancer cells that survive radiotherapy and thus promote increased spread of disease throughout the body. This fellowship aims to understand the complex biology that underpins this effect, and use this knowledge to identify novel treatments to use alongside radiotherapy to improve patient outcomes in the future. Objectives The initial phase of the fellowship gave important insight into the biology behind radiation driven invasion and from this identified potential chemotherapeutic inhibitors of radiation driven metastasis in two currently incurable cancers, glioblastoma and pancreatic cancer. The renewal period will expand on these findings through the following aims: 1. Further investigate the underlying science of radiation driven metastasis to expose new therapeutic vulnerabilities 2. Investigate the clinical impact that radiation driven metastasis may have on pancreatic cancer outcomes by drawing on the clinical expertise of key collaborators. 3. Develop novel therapeutic targets identified in the initial funding period towards the clinic. Applications and Benefits The continuation of this fellowship into the renewal phase will have applications across academia, public health care and industry. The key beneficiaries will be: 1) Academic The data generated from both the initial screens and validation experiments will be shared with the wider scientific community to help advance the cancer biology field. In addition, the models that are used to assess invasion and metastasis will be made accessible to other groups through collaborations and the provision of expertise. 2) Public healthcare services By understanding the clinical impact of radiation driven metastasis and its underlying biology, this fellowship will facilitate a better understanding of the potential risk/benefit of radiotherapy in different patient populations. This fellowship also aims to identify novel anti-metastatic therapies that can be used to negate any increased risk during radiotherapy to improve its efficacy. These outputs have a strong potential to influence how patients are treated in the future. 3) Commercial private sector beneficiaries The engagement of industrial partnerships will allow the successful translation of new therapies that have already been identified in the initial funding phase of the fellowship. 4) Wider population The major aim of the proposed research is to uncover new treatments to improve outcomes for patients with cancers that currently have dismal prognoses. This will hopefully lead to crucial improvements both to symptom management and survival rates
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