Gastrointestinal Cancer Biology Group

Dr Dan Worthley’s GI cancer biology group has been developing new preclinical models to manage gastrointestinal cancers, particularly bowel cancer. They have focussed on 3 main areas. Foremost has been the establishment of the Australian Living Organoid Alliance (ALOA), which is a network of Australian researchers including SAHMRI, WEHI and Monash, to coordinate national, multi-institutional colorectal organoid research and practice across Australia. Organoids are a living, preclinical bridge to allow validation of new cancer targets and new cancer therapies in the lab. We hope to establish an accredited laboratory in the near future that will allow individual patients to have their tumours tested for sensitivity against different chemotherapeutic options being tested in the lab, before being treated in the clinic. SAHMRI will also be focussing on growing organoids from benign bowel polyps to identify new ways to prevent the development of bowel cancer in the first place. Secondly, we have a number of mouse models of bowel cancer that we study in our mouse colonoscopy suite and theatre in the state of the art SAHMRI animal facility. We plan to run randomised controlled trials in our mouse hospital shortly. Finally, we are interested in the cells that support cancer growth, the surrounding cancer-associated fibroblasts. Utilizing a number of approaches we are identifying an activated mesenchymal signature, to suggest new treatment targets in the stroma, the surrounding tissue that acts as an accomplice to cancer growth. In another stream of research, we have a number of projects studying other stromal tissues, in particular the bone and cartilage and osteoarthritis. On first glance, this seems an unusual fit for a gastroenterology laboratory, but it highlights the common relationship of different clinical diseases to fundamental scientific areas such as stem cell biology. Having discovered two new connective tissue stem cells, one in the bowel and one in the bone, has allowed us to fund and study seemingly disparate fields of skeletal and intestinal disease.