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EPSRC IRC in Targeted Delivery for Hard-to-Treat Cancers

 
Cancer survival rates

BACKGROUND

The Engineering and Physical Sciences Research Council (EPSRC) Interdisciplinary Research Collaboration (IRC) in Targeted Delivery for Hard-to-Treat Cancers was established in October 2018 following the award of a £10M grant by the EPSRC to a consortium of five universities (Cambridge, Imperial, UCL, Glasgow & Birmingham) to develop new technologies to effectively deliver drugs for the treatment of four hard-to-treat cancers: mesothelioma, glioblastoma, ependymoma & pancreatic cancer.

 

THE CHALLENGE

The survival rate for most cancers doubled over the last 40 years, with 50% of patients surviving ten or more years. However, for hard-to-treat cancers the survival rates remain below 14% (see above, data from Cancer Research UK https://www.cancerresearchuk.org/health-professional/cancer-statistics-f...).

 

For brain cancer the standard treatment is surgery with chemotherapy and/or radiotherapy. However, many chemotherapy drugs only poorly penetrate the blood brain barrier, leading to sub-therapeutic concentrations of drugs at the tumour site. Similar problems are encountered in pancreatic cancers, the most common being pancreatic ductal adenocarcinoma (PDAC). One of the hallmarks of PDAC is the formation of rigid fibrotic tissue (stroma) around the tumour which impedes treatment by reducing the access of drugs and immune cells.

 

Malignant mesothelioma is an incurable cancer of the lining of the lung, caused by exposure to asbestos, often decades previously. Continued use of asbestos in many countries means mesothelioma will become a global health threat during this century. Operative removal of mesothelioma is rarely possible, and when attempted requires removal of the whole lung and pleural lining of the hemithorax.

 

The challenge is to increase cytotoxic drug concentration within the tumour whilst avoiding off-target toxicity. Two issues arise: (i) traditional targeted delivery strategies suffer from limited payload capacity of the delivery vehicles; and (ii) to access the tumour the drug needs to cross endogenous barriers: these include the blood brain barrier and tissue stroma.