Project case study 1: the HNC cell lines

Between 2007 and 2012 Heads Up funded a pioneering cancer research group at the University of Oxford. Headed up by principal scientist, Dr Stephan Feller, the HNC Research Group focused on head and neck cancer (HNC) cells to identify and understand the key molecules that bring about the development and spread of the disease.

‘In the stone age’ is the way Dr Feller describes our current understanding of cancer and corresponding therapies. At present, medical staff treating HNC patients seek to remove tumours through surgery and eliminate or reduce further spread of cancerous cells through radiotherapy. Chemotherapy, which is very successful in other cancer types, plays a minor role because no highly effective treatments have emerged to date.

Dr Feller is clear that we still have an enormous amount to learn about cancer, and he’s equally convinced about the need for improved treatment methods. Having lost his own grandfather to HNC, Feller has witnessed first-hand the devastating effect that such a cancer diagnosis can have.

The HNC cell lines

The last 10 years have seen the development of new technologies that enable us to study defects in individual cancers at a molecular level. Incredible as it may seem, until recently the vast majority of studies aiming to find new drugs and drug combinations have looked at only a handful of ‘cell lines’ grown from patient biopsies. These studies have been used to draw conclusions about drug sensitivity of a specific tumour type. Given our new knowledge about the massive diversity of tumour defects and their lack of commonality, it’s clear that to extrapolate results from only a couple of cell lines and offer patients generalised treatment is woefully inadequate.

Compared to other cancer types, it is relatively easy to generate permanent cell lines from the squamous (flat, plate-like surface tissue) carcinoma cells of HNC patients. This, combined with the large number of HNC patients treated at Oxford’s John Radcliffe Hospital, has meant that the Group has succeeded in gathering what is probably the largest collection of HNC cells in the UK.

The HNC cell line collection has enormous potential. It provides us with the opportunity to better understand the range and combinations of DNA/protein mutations in HNC patients and, in the very long term, we would hope that it could help lead to the development of a personalised treatment plan for every patient. True, this sort of therapy is a long way off, but in an ideal world we would hope that at some point every patient could have their tumour’s DNA and proteins fully sequenced to identify their own set of defects, enabling us to provide them with their own unique cocktail of drugs.

Raising the profile of HNC

As a small group of cancers, HNC is rarely on the minds of commercial drug developers. Thanks to Dr Feller’s extensive collection of cell lines his team has been able to gain access to the new drug candidates at a very early stage and test them in the laboratory to determine if some of the lines, or even most of them, respond to a particular new drug candidate. If a striking effect is detected, the team communicates their results to oncologists and encourage them to include HNC patients into trials early on. For example, the HNC Research Group has initiated an investigation to analyse the effects of the new anti-Survivin drug candidate on cells from our collection. This has revealed molecular actions that support the supposition that HNC patients should be included in future trials of anti-Survivin drugs.

 

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