The first of the NCRI's two plenary speakers on Tuesday morning was Simon Boulton from the Cancer Research UK London Research Institute. Although still relatively young, Boulton has received numerous awards for his ground-breaking work investigating mechanisms of genome stability and DNA repair,. He was awarded the EMBO Young Investigator's Award in 2007, became a member of EMBO in 2009 and has just received the EMBO Gold Medal.

Boulton started his talk with a clear explanation of the two mechanisms for the repair of double-strand breaks in DNA, non-homologous end joining and homologous recombination. His group studies these mechanisms using the nematode worm C. elegans as a model system. This tiny creature is the only multi-celled organism to have a complete cell fate map, and it is very commonly used as a model system in genetics and to identify new proteins and mechanisms that are important in human disease. Boulton described the gene RTEL-1, which encodes a protein that protects DNA from "toxic" recombination events, Complete loss of this gene is embryonic lethal, and its down-regulation is associated with the loss of the protective telomeres at the chromosome ends; it is a susceptibility gene for some types of cancer. Another example he used is a DNA helicase, HelQ, which has been implicated in Fanconi anaemia, an inherited disorder associated with a greatly enhanced risk of some cancers. Cells from HelQ-/- knockout mice are exquisitely sensitive to DNA damage agents, and genome-wide association scans have linked some HelQ variants to cancers of the upper aero-digestive tract.

The topic of the day's second plenary, given by Michael N. Hall from the Biozentrum, University of Basel, Switzerland, was an enzyme important for cell growth that is known by the name of its ligand. Target of Rapamycin (TOR) is a serine-threonine kinase that was first discovered in yeast and has been found conserved in all eukaryotes. Its function is to control cell size; cells in which TOR is down-regulated are small, and although knock-outs are embryonic lethal, flies in which TOR is universally down-regulated look normal but smaller overall than wild type flies. This effect is due to reduction in the size of individual cells, rather than in cell number: TOR is involved in normal physiological events that alter the size of organs, such as heart muscle growth after exercise. It is, however, therefore likely to be involved in cancer-related cell growth.

In both yeast and mammals, TOR is known to interact with a number of other proteins to form two different functional complexes, known in mammals as mTORC1 and mTORC2. These are activated through different mechanisms. mTORC1 is known to be activated by amino acids, cellular energy and growth factors; mTOR2 also appears to be regulated by growth factors, but through a different and more complex mechanism. Hall used a genetic screen to identify a protein called NIP7 as an upstream regulator of yeast TORC2 and then its mammalian equivalent, mTORC2. This is required for the assembly of the large (60S) ribosomal subunit but is nor part of the ribosome. Further work showed mTORC2 to act when directly associated with ribosomes bound to the endoplasmic reticulum as a critical regulator of cell growth.

The plenary lectures were followed by four parallel symposia, covering metabolism and cancer, the tumour micro-environment, the epithelial mesenchymal transition, and screening and prevention. This last named was particularly wide-ranging, including genome-wide association studies, specific screening interventions and public health. Malcolm Dunlop from the University of Edinburgh linked these by suggesting that individuals could be stratified by genetic risk for colorectal cancer, with individuals genotyped to be in high risk groups (who may well have many low risk alleles rather than a single, rare, high-risk one) being targeted for more invasive interventions. Martin Wiseman from World Cancer Research Fund International, based in the UK, presented two reports summarising systematic reviews of the evidence for diet and lifestyle interventions to cut cancer risk. While the results were not new – the meta-analysis underlined the usual recommendations, also highlighted by John Potter on Sunday, for a low-fat diet rich in plant foods and for physical activity – he stressed that individual action to change behaviour is likely to be partly successful at best without action by governments, health professionals and others to make "anti-cancer lifestyles" achievable by all.

Afternoons at NCRI conferences are set aside for a varied programme of parallel sessions, some grouped around set conference themes and others selected from submitted abstracts. One of the parallel sessions marked the twenty-fifth anniversary of the nuclear accident at Chernobyl with a series of papers devoted to the epidemiology and outcomes of radiation-induced thyroid cancer. This could be seen as particularly timely in the aftermath of the accident at the Fukushima power plant in Japan; a satellite symposium organised by the Chernobyl Tissue Bank is planned for Wednesday afternoon, after the end of the main meeting.

The “proffered paper” sessions included a further series of results from a full range of recent clinical trials. Two interesting Phase III trials were presented by David Ferry from New Cross Hospital, on behalf of the British Thoracic Oncology Group, and Robert Coleman from the University of Sheffield. Ferry described a three-arm study comparing carboplatin to two different concentrations of cisplatin in combination with gemcitabine for advanced non-small cell lung cancer. The motivation for this study was previous meta-analyses suggesting that carboplatin was inferior to cisplatin in this patient group. This trial, however, found carboplatin to be non-inferior in efficacy to, and less toxic than, the optimum higher dose of cisplatin: the lower dose of cisplatin was less effective. Ferry proposed that the inferiority of carboplatin reported in the literature might be due to difficulties in determining its dosing.

Breast cancer patients are sometimes prescribed bone-preserving bisphosphonates with chemotherapy, as they protect against fractures and may have an indirect effect on tumour cells. Coleman presented results of the AZURE trial of zoledronic acid with standard adjuvant chemotherapy in stage II/III breast cancer, Although zoledronic acid provided no additional benefit in the whole population of 3360 patients, a significant  benefit was observed in women well past their menopause (had not had a period for five years). Coleman suggested that larger trials to confirm the benefit of bisphosphonate treatment in this group of patients would be useful.

The day ended with two further plenary lectures. Both were given by distinguished clinicians, and both were engagingly presented, which delegates tired after two full days undoubtedly appreciated. Firstly, in a lecture punctuated with gardening metaphors and stunning photos of gardens, Eva Grunfeld from the University of Toronto, Canada, discussed the pressing issue of cancer survivorship. There is a large – currently estimated at over 22 million worldwide – and growing population who have finished treatment for and are living with the aftermath of cancer. These patients still need care, although it is generally recognised that in most cases this can be given as well, and more cheaply, by family physicians as by specialists. Many countries are rolling out so-called “survivorship care plans” laying out exactly what patients can expect from their doctors and what they should watch out for. Grunfield carried out a clinical trial of one type of care plan alongside standard best practice in patients recovering from early breast cancer and found no difference in quality of life between women who did and did not receive these plans. She described this result, however, as a “negative trial with a positive message” in that these patients were relatively well and may not have needed an additional intervention. Survivorship care plans may be more valuable in patient groups with more complex care needs.

Murray Brennan of Memorial Sloan-Kettering Cancer Center, New York, USA, presented a surgeon's view of cancer care in 2011, aiming to show that it should be disease- rather than discipline-based. He started with a lightning tour of the history of cancer treatment, from the earliest days when surgery was essentially the only treatment available through the beginnings of radio- and chemotherapy. Cancer care is now multidisciplinary, and collecting data from case series in databases (such as his own database of sarcoma cases) can provide useful results in the absence of trial data. However, fragmentation of cancer care by discipline can mean individual patients being treated by a disparate group of specialists, which is costly and confusing for the patient. With the cost of cancer care spiralling out of control, particularly in the USA, it is increasingly important to focus on realistic and cost-effective interventions. Brennan proposed strongly that a single physician taking overall responsibility for each individual case would be a useful step forwards.