Project case study 2: “kinobeadsTM”

The main focus of the Head and Neck Cancer Research Group headed up by Dr Stephan Feller, and funded by Heads Up between 2007 and 2012, is research into certain cell proteins that are known to drive the development of cancer growth and spread (metastases). Proteins make up roughly 20 per cent of cells; they fulfil a wide range of functions and have huge structural diversity. Examples of cell proteins include: haemoglobin which carries oxygen in red blood cells, and enzymes, which help speed up chemical reactions. Most relevantly to head and neck cancer (HNC) research, proteins also have an important role to play in facilitating cell division, growth and migration.

By better understanding certain proteins we hope to be able to seek ways to control and halt the growth and spread of cancerous cells. Through national and international ties that reach to Japan, Finland, Germany and the USA, the HNC Research Group has pinpointed several new proteins, known as protein kinases, as having candidate targets for developing new types of molecular HNC therapies.

Like all proteins, kinases have ‘binding sites’: areas on their surface that provide an exact fit with another protein of a specific type, just like a key fits in a lock. Since pharmaceutical companies can make good kinase inhibitors (chemicals that fit exactly onto a specific kinase’s binding site and stop its action as an enzyme), a better understanding of the role of kinases provides the potential for the development of future therapies that will reduce or halt the growth and spread of cancer in patients.

The big idea

While attending an academic conference, Dr Feller learnt about a cutting edge technology known as Kinobeads ™, in which beads coated with multiple drug-like molecules can be used to systematically fish for protein kinases. Reflecting on the technology, Dr Feller had the idea of using it to pull out the kinases from our collection of HNC cell lines in order to find out which kinases are produced at more than normal levels in subsets of HNCs.

‘There is currently only one academic team in the world with unrestricted access to the Kinobeads™ technology. It is based at the Technical University in Munich, headed up by Professor Bernhard Kuster, and they’ve agreed to work with us. We bring the unique cell collection and the initial idea; they bring the tools’, says Dr. Feller. ‘The first promising leads for kinases that could drive different subsets of HNC are now under scrutiny. The current technology has allowed us to screen ca. 300 of over 500 existing kinases and as the technology evolves we may be able to study even more.

We were also pleased to note that our recent publication of the results in a high profile international proteomics journal has gained considerable international attention, for example by the American Society for Biochemistry and Molecular Biology (ASBMB)”.

Clinical trials

Now part of an Oxford-based, multi-disciplinary phase I clinical trial team, the HNC Research Group is scheduled to conduct and monitor a phase I a/b trial sponsored by Cancer Research UK that opens in 2012. The trial will explore a new drug from AstraZeneca (AZD0424) that inhibits Src family kinases which are important for the survival, proliferation and/or migration of HNC cells, specifically in tongue squamous carcinomas, the most frequent form of HNCs. Given the scarcity of funding, it is great to know that this trial project has recently met CRUKs stringent evaluation criteria and has been approved for further funding.

Over the next six months Dr Feller plans to work with animal specialist, Dr J Li, to treat mice with AZ drug and to analyse its effects on tumour cell proteins targeted by Src family kinases. If successful, this will validate a new type of ‘biomarker assay’ that will allow us to better monitor the effects of the drug in tumour biopsy tissue from trial patients.

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