by ecancer reporter Clare Sansom

Morning Session

The first full day of the NCRI conference kicked off with a pair of plenary lectures given by research leaders from the same institute: the world-leading Dana-Farber Cancer Institute in Boston, Massachusetts, USA.

Kenneth Anderson was the first to speak. He described one of the more remarkable success stories of translational cancer research: the discovery and development in the last decade of eight novel agents for multiple myeloma, which togetther are transforming the prospects for patients diagnosed with this condition. These new drugs target a range of molecular targets, many of which have only been validated in recent years.

Some well-known drugs are less effective in myeloma than in other tumour types because myeloma cells are protected by the bone marrow stromal cells that form their micro-environment. Drugs that kill myeloma cells despite this protection include those that target the proteasome, including bortezumib. In one trial, a combination of bortezumib with two other targeted therapies, lenalidomide and dexamethasone, achieved an almost unprecedented 100% response rate.

Other recently induced novel drugs include antibodies and other immune-based agents and bromodomain inhibitors. These act by suppressing gene expression by modifying chromatin. Anderson ended his talk by presenting the mutational spectrum of multiple myeloma. Complete cures in myeloma are and will probably continue to be rare, but Anderson's stated aim of turning it into a chronic disease may not be far off.

The theme of mapping the genetic landscape of cancer was continued by Judy Garber, who gave the second plenary lecture. Her work, like Anderson's, relies on exceptionally close collaboration between basic scientists and clinicians: not just from bench to bedside but back again. Genetic screening for cancer predisposition is becoming more prevalent in rare as well as common cancer, even though the majority of familial variation in cancer risk is still unaccounted for.

The plummeting price of whole genome sequencing is already having a profound effect on cancer genetics. Many clinical studies now routinely include the sequencing of tumour and matched normal tissue from cancer patients. While the tumour genetics will primarily interest those patients, the normal tissue will yield information about somatic mutations that may be equally important for their families. Cancer genomics is likely to revolutionise clinical practice, but there are important ethical implications that must be thought through.

Later in the morning, these themes of genetic profiling and personalised medicine were continued in an interesting and very well-attended session on trends in cancer drug development, chaired by Susan Galbraith from Astra Zeneca in the UK. 

Afternoon Session

One characteristic feature of the NCRI's cancer conferences is the wide range of research presented, from basic molecular biology through to clinical practice. The first full day of the 2012 meeting ended with two contrasting plenary lectures that highlighted this range of disciplines.

The first was given by Eduardo Bruera from the University of Texas MD Andersen Cancer Center, Houston, USA. Bruera is a world-leading clinician scientist in palliative medicine and his topic was simply “Cancer Pain Control”. About eighty percent of patients with advanced cancer suffer from pain, and it is one of the most distressing cancer symptoms for both patients and their families. Pain, however, is subjective; clinicians can only ever know what their patients tell them about their pain, and levels of pain experienced depend on, for example, whether a patient is fatigued or depressed. Furthermore, although much pain does arise directly from signals from the tumour (nociception), it can arise from unrelated health problems or even from therapy. A patient whose pain is mainly caused by the tumour will respond better to analgesics than one with the same level of perceived pain with a more complex origin,

Bruera then moved on to discuss developments in analgesia for cancer pain. Corticosteroids, opioids such as methadone, slow release analgesia and cycling between opioids can all improve cancer pain control, but clinicians must remember that even impeccable assessment and treatment of pain will not remove it completely in advanced cancer.

The second plenary was given by Lee Helman from the National Cancer Institute, Bethesda, Maryland, USA. In contrast, this focused on the basic molecular biology of the paediatric tumour rhabdomyosarcoma (RMS). Helman began by describing the identification of the gene CRKL as necessary for the growth of RMS cells in vitro and in vivo. This gene is over-expressed in cells from both main RMS subtypes but not in the muscle cells from which this tumour is derived. As CRKL encodes a protein that binds phosphotyrosine, Helman and his group explored its interaction with signal transduction pathways. They discovered that it interacts with src kinases, particularly those in the YES sub-family. YES kinases are also strongly expressed in RMS cells, and blocking this signalling pathway with dasatinib and other src inhibitors prevented RMS cell growth,

Helman went on to discuss the role of IGF1R signalling in RMS, and showed that this pathway does not interact with CRKL / YES signalling in this disease. Combinations of antibodies against IGF1R with src kinase inhibitors work additively to completely suppress RMS cell growth in vitro. The work has now moved into in vivo studies and this combination of agents may prove effective against this aggressive paediatric tumour.