Targeting radiation driven invasion and metastasis in cancers of unmet need

Radiotherapy is used for a number of cancers, and while it is an effective and potentially curative treatment, it can induce unwanted behaviour in cancer cells that remain following therapy. One such behaviour is the induction of increased invasive potential, allowing cancers cells to disseminate and metastasise into normal tissue thus contributing to treatment resistance and recurrence.

This project aims to identify new therapeutic avenues that can be used alongside radiotherapy to contain metastatic spread in three cancers: glioblastoma, colorectal cancer and pancreatic cancer. These cancers are currently of unmet need and novel, innovative therapies are urgently required to improve outcomes and survival rates. The work proposed will further our understanding of the processes that drive invasion and metastasis in these cancers, leading to the identification of novel anti-invasive, chemotherapeutic targets to improve patient outcomes in the future.

Radiotherapy is the standard of care (SOC) for a large number of cancer types, and although an effective treatment, its potential to generate unwanted pro-metastatic phenotype in remaining cancer cells needs to be carefully managed to maximise treatment success. The proposed research has the potential to generate both novel mechanistic insights into the processes that underpin radiation driven cancer invasion and metastasis, but crucially, to also identify new therapeutic avenues in three cancers of current unmet need; glioblastoma, pancreatic and colorectal cancer, that can be used alongside current SOC to improve patient outcomes in the future.
The key beneficiaries will include:
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
One of the major potential outputs of the proposed research is the identification and pre-clinical validation of new chemotherapeutics for use alongside standard of care. Different radiotherapy regimes and advanced imaging will also be investigated using state of the art pre-clinical in vivo models. These outputs have a strong potential to inform clinical management of cancer patients in the future.
3) Commercial private sector beneficiaries
The engagement of industrial partnerships will be paramount to the successful translation of any identified therapies to the clinic. Industry collaborators will be secured at pertinent stages of target development.
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