Skin cancer arises due to the development of abnormal cells that have the ability to invade or spread to other parts of the body. There are three main types: basal cell cancer (BCC), squamous cell cancer (SCC) and melanoma. Greater than 90% of cases are caused by exposure to ultra-violet (UV) radiation from the sun. This exposure is increased in Australia due to a large hole in our ozone layer, directly above. Thus, skin cancer accounts for 80% of all new cancers diagnosed each year in Australia, with Australians having the highest rate of melanoma in the world.
Established approaches to treat melanoma are largely ineffective, due to the genetic mutation in melanoma (highest of all cancer types). This has led to extensive research into understanding melanoma at a genomic level and the surrounding normal tissue and vasculature that dictate the invasive capacity of a patient’s unique tumour mass.
2D experimentation (cancer cells in a petri dish) is the most common research method initially undertaken to understand the cytotoxic or inhibitory effect of novel compounds on cancer cell death. However, this does not accurately model the complex three-dimensional environment of cancer invasion and spread (also known as metastasis), as occurs in the human body. Cancer invasion and metastasis are influenced by the surrounding normal cells, governing individual and collective cell behaviour. The cancer microenvironment contains lots of different cells, like white blood cells and vascular cells, as well as proteins that make up the scaffolding for the cells within a specific tissue area. Thus, this microenvironment constitutes the backdrop on which the hallmarks of every patients cancer can evolve.
In order to control a malignancy, it is therefore necessary to target and control the growth, invasion and spread of the cancer cells through modifications within this microenvironment. In order to further understand the crosstalk between skin cancer cells and this microenvironment, this project will examine the impact of the microenvironment within a 3D setting, allowing us to examine the aberrant regulation of critical events that lead to the first cancer cells separating and metastasising from the primary tumour.
Through using this 3D tumor invasion model, in conjunction with advanced imaging techniques, we are discovering detailed mechanistic information on tumour invasion, migration and drug response. This powerful novel system emulates the environment that occurs in the human body during cancer growth and invasion. Thus, this technique will allow for drug response testing on specific patient tumour samples, allowing us to gauge treatment effectiveness upon cancer cell migration within patient specific cancer states.
Finally, understanding skin cancer at a genomic level, will allow for an increased understanding in drug response prediction. This project will utilise genome sequencing technology to annotate the specific gene mutations of patient skin tumour samples and store these onto a database. This database will also collate the effectiveness of both conventional and novel targeted therapies upon skin cancer cell migration. Thus, this project will help to improve treatment options for each specific skin cancer patient and provide essential data for more effective treatment plans for future skin cancer patients.