by ecancer reporter Clare Sansom

Each year, the NCRI presents results from important recent clinical trials in cancer in a “showcase”.

The 2013 Clinical Trials Showcase was split into two sessions, both presented on Tuesday 6 November.

Introducing the first session, its chair, Matt Seymour from the NIHR Cancer Research Network in Leeds highlighted the number of trials now taking place in the UK; each week, 1000 new patients are enrolled in clinical research projects here, with 400 of these entering randomly controlled clinical trials.

John Bridgewater of University College London Hospitals Trust presented results from the new EPOC study, a Phase III trial testing the addition of cetuximab to standard chemotherapy in patients with operable lung metastases from colorectal cancer.

A total of 233 patients with this condition and wild type KRAS were randomised to receive either standard chemotherapy or standard chemotherapy plus cetoximib for 12 weeks before and 12 weeks after liver resection; patients in both arms had similar characteristics and received similar chemotherapy regimens.

Significantly more patients responded before surgery in the cetuximab arm.

However, progression free survival was significantly worse in the cetuximab arm, with a median progression free survival of 14 months compared to 20 months for those patients who received chemotherapy only.

The reasons for this surprising and disappointing result are still unclear, but it may be that cetuximab function is compromised by further mutations in proteins in the EGFR pathway.

After the showcase, Stephen West from the Cancer Research UK London Research Institute presented the first of Tuesday's plenary lectures, on the theme of DNA strand break repair.

The DNA in each of our cells is damaged thousands of times a day and cancer-causing mutations will accumulate if this damage is not repaired.

Double strand breaks are relatively rare DNA lesions that mainly arise during DNA replication, and they must be repaired accurately to maintain genome stability.

Two distinct types of double strand break repair mechanism have evolved; homologous recombination, which takes place during replication using the sister chromatid as a template for the repaired strand, is by far the more accurate.

West's lecture focused on the structures and mechanisms of some of the proteins involved in this mechanism, including proteins known to be mutated in cancer predisposition syndromes.

His group's work has led to the discovery of the mechanism of the well known breast cancer predisposition protein BRCA2.

This protein was found to act as a chaperone, binding to another homologous recombination protein, Rad1, and ensuring that that protein binds to single-stranded rather than double-stranded DNA.

Women with Rad1 mutations are also at increased risk of breast cancer.

West also described mechanisms through which cells repair covalent links between DNA strands known as Holliday junctions, which arise when homologous recombination occurs from both ends of a strand break at once.

Mutations in the BLM gene, which encodes a protein involved in the most efficient Holliday junction repair mechanism, are responsible for Bloom syndrome.

This rare disease has been described as “the ultimate cancer predisposition syndrome” and individuals with BLM mutations have a greatly elevated risk of many different cancers.