Radiotherapy activated materials for enhanced cancer treatments

Cancer remains one of the most significant causes of mortality worldwide, with 8.2 million deaths and 14.1 million new cases reported in 2012 alone (World Health Organization, 2012: http://www.who.int/mediacentre/factsheets/fs297/en/), and a cost to the EU of 126 billion Euros in 2009. Chemotherapy is currently a major approach for treating cancer but a continuing concern is the inability to deliver therapeutic doses of drug directly to cancer cells without affecting normal cells. A new generation of medicines is needed to address the current shortcomings and to target complexities associated with differing cancer types, disease progression and tumour anatomies. The focus of this project is triple negative breast cancer (TNBC) which affects 12% of the 1.4 million newly-diagnosed breast cancer cases each year. There are very limited treatment options for TNBC because this form of cancer does not express any of the three biomarkers that are targeted by current therapies (including drugs such as Herceptin). For this Fellowship project we target TNBC with new chemotherapeutics which have been specifically designed to operate alongside radiotherapy, to exploit some changes in biology which occur during and after radiation damage. It is estimated that ~ 60% of cancer patients will receive radiotherapy, yet to date, chemotherapeutics have rarely been designed to recognise this clinical fact. The project will therefore explore a new and powerful means to combine radiation and chemistry to target cells which would otherwise evade therapy.

Impact from the Fellowship will arise through new materials for an important unmet medical need, but also through a change in 'research culture' for the Fellowship team. We are building on some established chemistries but with some new components specifically targeted to the therapeutic regimens currently in use in the clinic. One of the main drivers for impact will be the embedding of the Fellowship within the industrial pharmaceutical development pathway, such that lab formulations designed to exploit biological mechanisms observed in the clinic are rapidly taken to go/no go decisions in the industry context. Health economics and regulatory decisions are included in the efficacy review of the new materials from the start - a significant departure from normal academic lab end-points.

Outreach and Advocacy will involve the full Fellowship team. We have experience of science outreach (YouTube, Royal College of Art, Science Festivals) and will work with oncology experts including John Saunders and Breast Cancer Now to establish appropriate outreach mechanisms for the sensitive subject of cancer.

The medical needs for breast cancer are all too apparent, with > 1.4 million new cases per year, and ~ 200,000 in the Triple negative classes. In addition to the mortality and morbidity, the affects on patients' families, there are economic losses of ~£1.5 bn due to breast cancer in the UK alone. This project is aimed to have technologies fast-tracked to new medicines via the combination of radiobiology-inspired therapies and innovative chemistry formulations.
The project may in the long term also impact on other cancers such as non-small-cell lung cancers. The difficulties of delivering drugs to these cancers by inhalation have meant that many injectable formulations for treating lung cancers are being developed. These include Abraxane and BIND-014 (both in Phase II trials). However, neither Abraxane or BIND-014 have drug release mechanisms which take account of the changed biology of radiation treated cells. As with TNBC, there is a compelling case for new formulations of drugs which could be activated in radiation-treated cells.

Impact also lies in encouraging and retaining key skills and investment opportunities in the UK. Government figures show that the chemicals and pharmaceuticals sectors alone made up 1.9% of gross value added to the UK economy in 2011 (total value of chemicals and pharma ~ £27bn). This project will contribute to the increasing need for Advanced Materials in Healthcare Technologies: as noted in the recent EPSRC Materials Review "UK businesses that produce and process materials have a turnover of around £170bn pa, represent 15% of the country's GDP and have exports valued at ~£50bn. A real opportunity exists for the UK in developing materials designed for targeted applications, reducing lead times from discovery to market and focusing on sustainability." Pharmaceutical products are a vital part of any materials strategy, and the polymer-based implant cancer drug, Zoladex, is a key indicator of the need for continuing investment in biomedical materials. AstraZeneca have invested £120 million in a new facility at Macclesfield, UK plant to meet continuing global demand for Zoladex, which is one of the world's leading therapies for prostate cancer and is also indicated for breast cancer. It is currently AstraZeneca's fifth largest selling drug with annual sales of ~ $1 billion.
The Fellowship is informed throughout by a strong link to AstraZeneca, who will provide expertise and guidance on how to take a lab-based formulation towards a marketable and manufacturable product. The costs of a potential new breast cancer formulation will thus be evaluated against the existing best practice, and the potential for meeting a currently intractable medical need.