Sydney Cancer Conference 2014

Keynote Abstracts KN01: NEW INSIGHTS INTO P53 PATHWAYS FUNCTION Professor Sir David Lane p53 lab A*Star Singapore Our recent genome analysis studies on the p53 system’s evolution have shown that the p53 pathway has been conserved for over a billion years. We have identified p53 and Mdm2 proteins in many invertebrates, including very primitive organisms such as the Placozoa. Remarkably when these proteins are expressed in mammalian cells they retain a measure of their functions and interactions with each other . This extreme conservation is not easily reconcilied with the viability and normal development of mice that lack both p53 and Mdm2 genes nor with the loss of Mdm2 in Drosophila and Caenorhabditis species leaving one to conclude that the p53 Mdm2 axis must be involved in checkpoint or editing functions that are required for robustness of the organism. Building on this concept one can then assume that p53 mutant tumor cells may lack fidelity of duplication giving them an advantage in the development of resistance but also making them intrinsically sensitive to some challenges. In exploring this we have screened for drugs and treatment strategies designed to selectively eliminate cells that have lost p53 function while not damaging normal cells. In one approach we have developed peptides that can activate a growth arrest in normal dividing cells but not in p53 mutant cells leaving these cells selectively vulnerable to cytotoxic chemotherapy. In another approach we are seeking pharmaceutical inhibition of the p53 pathway to lessen the side effects of chemotherapy. Fundamental to these approaches is the need for a greater understanding of the balance of the p53 response between inducing apoptosis, growth arrest, senescence and repair. The tool compounds we are developing are advancing this understanding.

KN02: INTERCELLULAR COMMUNICATION IN EPIDERMAL CARCINOGENESIS Professor Fiona Watt King’s College London Multilayered epithelia such as the epidermis and oral mucosa are maintained by self-renewal of stem cells and differentiation of their progeny. By describing a mouse model of wound-induced tumour formation I will present evidence that both stem cells and differentiating cells can contribute to tumour development. I will describe how aberrant gene expression by differentiated cells can recruit stem cells, fibroblasts and cells of the bone marrow to collaborate to form tumours.

KN03: EVALUATING ACCESS AND QUALITY ACROSS THE CANCER CARE CONTINUUM Professor Eva Grunfeld Ontario Institute for Cancer Research and Department of Family and Community Medicine, University of Toronto Cancer research is in the vanguard of innovations in medical care such as personalized/stratified medicine. However, for the benefits of innovations in cancer care to be realized there must be a cancer care system that is able to adopt, implement, and sustain those innovations. Quality and access are two dimensions of care which determine the quality of cancer care services. In order to determine the extent to which access to quality cancer care occurs at a population level a systematic approach to operationalizing, measuring, and reporting those dimensions is required. This presentation will examine access to quality cancer services along the cancer care continuum (diagnosis, treatment, follow-up/survivorship care and advanced disease). Methods and metrics for determining quality (such as the use of quality indicators) and access (considering equity) at a population level will be described. Limitations and challenges will be discussed.

KN04: PLASMA DNA-BASED GENOMIC AND METHYLOMIC PROFILING IN CANCER AND PRENATAL DIAGNOSIS: TWO SIDES OF THE SAME COIN Professor Y. M. Dennis Lo Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong SAR, China Recently, there is much interest in the use of cell-free DNA in plasma for molecular diagnosis. In particular, tumour DNA has been found in the plasma of cancer patients and fetal DNA has been found in the plasma of pregnant women. My group has been pursuing both of these areas in parallel and has demonstrated synergy in this approach. In particular, we have demonstrated that plasma DNA analysis using massively parallel sequencing can be used for detecting a variety of fetal chromosomal aneuploidies, including Down syndrome. Such an approach can also be used for detecting cancer-associated copy number aberrations and single nucleotide variants. In addition, we have developed an approach for carrying out genome-wide plasma DNA bisulfite sequencing. This approach can be used for profiling the fetal methylome using the plasma of a pregnant woman. A similar approach can also be used for profiling the methylome of a tumour in the plasma of a cancer patient. We have shown that plasma DNA-based genomic and methylomic profiling can be used for detecting many types of cancer. Indeed, this method appears to have the potential to become a universal method for cancer detection and monitoring.

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SYDNEY CANCER CONFERENCE, 26 November 2014, The University of Sydney.

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