Role of the tumour microenvironment in gastric cancer

Gastric cancer (GC) is the fourth most common cancer globally and 7th in incidence in Australia. It has a poor survival rate which can be attributed to the advanced stage at diagnosis in most patients. The molecular and cellular mechanisms underlying the development of GC are not well described. Traditionally cancer research involved studying the cancer cell itself. More recently, there has been growing interest in studying the normal cells and molecules which surround the cancer cell. This tumor microenvironment consists of a variety of stromal cell types including cells such as fibroblasts. It is believed that the dynamic communication between tumor cells and the surrounding cell types may play a major role in cancer initiation, progression and establishment of metastatic disease. The aim of this project is to investigate tumor-stromal interactions in gastric cancer utilizing established and primary cell lines. Once the molecular pathways by which a tumor cell progresses has been elucidated it is possible that these processes could be exploited in the development of novel therapeutics. Our previous genomic experiments have provided a number of exciting candidate genes that may be involved in this interaction. This is novel research that may have a major benefit to our understanding of cancer and improve patient outcomes. We have access to a unique cohort of patient specimens with comprehensive clinical data. In addition we have developed novel animal model systems and in vitro tools which we use to answer our research questions. This project will use a broad range of techniques such as live cell microscopy, cell culture techniques (including organoids) and molecular biology to interrogate the function of gene products that influence tumour-stroma communication. This project may also involve the use of animal models. Relevant publications: 1. Busuttil R.A. et al (2014) A signature predicting poor prognosis in gastric and ovarian cancer represents a coordinatated macrophage and stromal-response. Clin Cancer Res; May 15;20(10):2761-72 2. Busuttil RA et al. (2018) An orthotopic mouse model of gastric cancer invasion and metastasis. Sci Rep. 2018 Jan 16;8(1):825. doi: 10.1038/s41598-017-19025-y.